• Users Online: 200
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 35-40

Prohibitin gene regulation in cancer and its possible therapeutic potential

1 Xcode Life Sciences, Chennai, Tamil Nadu, India
2 Department of Biosciences, Jamia Millia Islamia, New Delhi, India
3 Department of Laboratory Medicine, Albaha University, Al Bahah, Saudi Arabia
4 Department of Obstetrics and Gynaecology, MAMC, New Delhi, India
5 School of Biological Science, Apeejay Stya University, Gurugram, Haryana, India

Date of Submission11-May-2021
Date of Acceptance28-Jun-2021
Date of Web Publication31-Jul-2021

Correspondence Address:
Farah Parveen
Department of Biosciences, Jamia Millia Islamia, New Delhi.
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jco.jco_10_21

Rights and Permissions

Prohibitin (PHB), an evolutionary conserved gene, is mapped at the chromosomal location 17q21–q22 and is present with two isoforms, namely, PHB1 and PHB2. Both of these isoforms have their individual roles in tumor suppression and cell proliferation. The presence of these isoforms is not restricted to single cellular organelle but can be located in the nucleus, mitochondria, and cytosol. Importantly, loss of heterozygosity in the prohibitin gene has been noted in a significant number of different cancer types. Along with this, there are other mutations that contribute to tumorigenesis and cancer cell proliferation. Sporadic breast cancer, lung cancer, and prostate cancer are a few examples in which regulation of PHB plays a major role. PHB has shown to be both up-regulated and down-regulated depending on the type of cancer or disease. PHB acts as the biomarker for several types of cancers and is also seen as a potential therapeutic target. Along with cancer, PHB has also been seen to play an important role in other diseases such as neurological diseases, cardiac diseases, and renal diseases. The link between PHB and a plethora of diseases opens a new window in which PHB can be actually targeted in treatment as well as disease management. Here, we review the regulation of PHB in different types of cancers along with its significant interaction in other disorders.

Keywords: Alzheimer’s disease (AD), androgen receptor (AR), cancer, prohibitin (PHB)

How to cite this article:
Najm MZ, Sadaf, Akhtar N, Kashyap P, Shingatgeri VM, Sharma K, Raghav A, Rout VK, Parveen F. Prohibitin gene regulation in cancer and its possible therapeutic potential. J Curr Oncol 2021;4:35-40

How to cite this URL:
Najm MZ, Sadaf, Akhtar N, Kashyap P, Shingatgeri VM, Sharma K, Raghav A, Rout VK, Parveen F. Prohibitin gene regulation in cancer and its possible therapeutic potential. J Curr Oncol [serial online] 2021 [cited 2022 Aug 8];4:35-40. Available from: http://www.https://journalofcurrentoncology.org//text.asp?2021/4/1/35/322887

  Introduction Top

Prohibitin (PHB) gene has been known to play an important role in human cellular senescence and tumor suppression. It was originally found in liver cells of rat in which it expressed antiproliferative activity. In humans, this gene encodes for two isoforms of proteins in the form of PHB 1 and PHB 2 and it has a molecular weight of ~33 kDa[1],[2] that comes under stomatin/prohibitin/flotillin/Hflk/C (SPFH) family domain.[3] The N-terminal domain contains hydrophobic alpha helix that plays a role in lipid raft formation and helps in protein–protein interactions.[4] The localization of the prohibitin gene PHB1 is diverse in the cell organelle; when present in the inner membrane of mitochondria, it interacts with PHB2 and stabilizes the mitochondria which later is involved with apoptosis.[5],[6] PHB1 present in the plasma membrane interacts with viral and other microorganisms and acts as receptor for entry into host cell.[7] PHB1 located in lipid raft of the plasma membrane interacts with Raf-1 and activates it. Raf-1 being oncogene activates ERK and leads to cancer progression.[8] In contrast, PHB2 localized in the membrane has been found to have a role in cancer cell migration.[9] In the nucleus, PHB1 binds to various transcription factors, such as PHB1 located in p53, E2F, and pRb.[10] PHB2 in the nucleus is involved in the protection of centromeric cohesion and promotes cell growth. After several studies and researches, it has been identified that this gene has significance in tumorigenesis, cancer cell proliferation, metastasis, and apoptosis.[11],[12],[13],[14] The functional domains of prohibitin, namely, retinoblastoma (Rb) and E2F domains, have been found to be frequently mutated, leading to breast cancer development.[12] This review includes how mutations in the prohibitin gene alter regulation in carcinogenesis and tumor growth in humans.

Prohibitin is well investigated to be the negative regulator of cell cycle progression and controls E2F transcriptional factor.[10] Modifications at the time of DNA replication and transcription in the gene are known to cause mutations that eventually result in cancer. In prostate cancer which is linked to the androgen receptor (AR), overexpression of PHB represses AR-induced gene activation which helps in suppressing the growth of tumor in AR-dependent LNCaP xenografts.[13] In prostate cells, 5-alpha-reductase converts testosterone into dihydrotestosterone. AR being a ligand-activator transcription factor, when it binds to the androgen (e.g., DCT), it mediates androgen responses.[9],[11] Further, in ER-positive breast cancer, the PHB plays a significant role by activating AR leading to potential molecular targets for breast cancer treatment.[14] In the 3'-untranslated region (3'-UTR) of the prohibitin gene, mutation at position 729, i.e., single nucleotide polymorphism in the breast cancer cells, results in the formation of a variant T allele that lacks antiproliferative activity of C allele.[15],[16] This observation later concluded as women with T allele have more susceptibility toward breast cancer.[13] Moreover, both PHB1 and PH2 have shown to play roles in cancer cell proliferation, cancer cell metastasis, and cancer cell apoptosis.[16] It is important to note that apart from breast cancer, none of the somatic mutations was identified in ovary, liver, and lung cancer.[2]

  Prohibitin Gene Top

Prohibitin is a special class of proteins and is highly conserved in nature. The human genome encodes two proteins: PHB 1 and PHB 2. They function independently as heterodimeric complexes and are found to have a significant role in transcription, cell division, and membrane metabolism and thus are key regulators in effect of cancer and other metabolic diseases.[1] Prohibitin, which is a chaperone protein, displays potency of an antiproliferative role. Studies suggest that 3'-UTR of the PHB gene encodes a functional RNA. This arrests the proliferation of the cell cycle between G1 and S phase.[15] Prohibitin gene is found to repress cell growth. This is achieved by modulating E2F transcriptional activity.[12] To add more, prohibitin also regulates transcription by remodeling chromatin molecules.[17] The dual modulating transcriptional function of prohibitin reveals its association with p53, an established tumor suppressor gene, binding to its consensus DNA site.[18],[19]

  Localization of the Gene Top

Studies suggest that PHB1 and PHB2 localize in the nucleus, mitochondria, and cytosol of the cell [Figure 1].[20] PHB proteins depend on mitochondrial functions. Both PHB1 and PHB2 assemble at the inner membrane of mitochondria in order to form a supra macromolecular structure. This structure works as a scaffold for lipids and proteins and thus regulates mitochondrial metabolism.[21] In the nucleus, PHBs modify DNA associated enzymes, transcriptional factors, co-regulators, and receptors.[1] Whereas in cytosol, they interact with proteins associated with cytoskeletal transport and cellular signaling.[1] Studies suggest that the primary function of PHBs is restricted to mitochondria only.[22] They are expressed in high energy demanding cells which are more susceptible toward mitochondrial dysfunction. It targets the N terminus and signals for nuclear localization at the C terminus. Whereas in case of PHB1 in humans, the N terminus does not possess mitochondrial targeting sequence.[23] PHB is one of the potential substrates for Akt. Akt/protein kinase B-dependent phosphorylation of PHB1 at Thr258 leads to mitochondrial translocation of the protein.[24] This phosphorylation of PHB leads to transcriptional regulation of E2F protein and further activates Ras-Raf pathway.[25] Localization of prohibitin in the mitochondria and nucleus along with crucial binding partners is shown in [Figure 1].
Figure 1: Localization of prohibitin in the mitochondria and nucleus along with crucial binding partners

Click here to view

  Mutations in Prohibitin Top

Mutations in the prohibitin gene have shown their role in tumor development. In a study, it was found that normal prohibitin was able to bind with retinoblastoma tumor suppressor protein and its family members p107 and p130, which interact with E2F family of transcriptional factors while the mutant prohibitin did not.[26] The gene location of prohibitin is 17q21, in which loss of heterozygosity was found to have a role in sporadic breast cancer and was also found to be inheritable.[27],[28] In a study in India on 105 breast cancer patients, it was found that the expression of prohibitin is different on the basis of mutation, thus proving the association of prohibitin gene with the development of cancer.[29] According to a study, it was found that prohibitin is overexpressed in papillary thyroid carcinomas bearing BRAF (V600E), in which BRAF is an oncogene.[30] The overexpression of prohibitin could be the mechanism to overcome the negative effect of the BRAF oncogene.

  Role of Prohibitin in Cancer Top

Many studies have shown a direct relation of loss of heterozygosity at chromosome 17q21, a region found to be frequently mutated in sporadic breast cancer.[12],[27],[28],[29] A study has shown that overexpression of prohibitin is seen to have relation with prostate cancer.[31] Another study has shown overexpression of prohibitin to be directly related to prostrate cancer and bladder cancer.[32] To add more, one study exhibited the relation between loss of prohibitin and ovarian cancer.[33] Prohibitin also has binding sites for micro-RNA-27a (miR-27a), which is linked to overexpression gastric cancer[34] and also hepatocellular carcinoma.[35] The promoter region of PHB1 contains consensus binding domains for Myc oncoprotein that can lead to overexpression in different cancer types.[33],[36] PHB1 has also proved to be a tumor suppressor in hepatocytes.[37] By interacting with p53, PHB1 has also shown to inhibit proliferation of human osteosarcoma.[38] In nasopharyngeal carcinoma, PHB1 is found to be down-regulated.[39] Down-regulation of PHB1 has shown to inhibit cancer cell proliferation in esophageal squamous cell carcinoma.[40] In the hypoxic tumor microenvironment, PHB2 has been observed to contribute to hepatocellular carcinoma growth and malignancy progression.[41] Inhibition of PBH2/repressor of estrogen receptor activity (REA) transcription complex was observed in estrogen-dependent carcinomas.[42] In a study, it was noted that PHB1 is frequently overexpressed in lung cancer cells.[43] Similarly, PHB1 and PHB2 have proved their roles in several cancers, cancer cell metastasis, and cancer cell apoptosis.[9] Overall, prohibitin’s expression is not always down-regulated and at the same time is not always up-regulated while analyzing different cancer types and the gene can thus be placed in dual category, possessing anti- and pro-tumorigenic activities.[44] The expression pattern of PHB in various types of cancer is shown in [Table 1].
Table 1: Expression of PHB in different cancer types

Click here to view

  Prohibitin’s Role in Oxidative Stress and Other Diseases Top

The imbalance in the production and accumulation of reactive oxygen species in cells and tissues and body’s ability to detoxify it is known as oxidative stress.[53] It is known from previous reports that PHB1 has a function in resisting oxidative stress in various cell types. The level of PHB1 is reduced during the oxidative stress in epithelial cells of the intestine[54] and also in ex vivo lung tissue in case of hyperoxia.[44],[55] The vital link of PHB with oxidative stress is noted due to the relation between oxidative stress and the development of neurodegenerative diseases,[56],[57] such as Alzheimer’s disease (AD), Parkinson’s disease (PD), diabetes mellitus,[58] atherosclerosis and cardiovascular diseases,[59] metabolic syndrome, and skin and tumor diseases.[60],[61] In future, deeper analysis of the role of PHB in oxidative stress would open a new therapeutic window in treating various diseases.

  Therapeutic Application of Prohibitin in Cancer Top

Prohibitin acts as a potential biomarker for tissue-based interactions of gastric cancers. This detection is carried using immunohistochemistry and real-time PCR.[53] It targets tyrosine target signaling. Once activation of insulin receptors is achieved, cytoplasmic domain modifications take place including auto-phosphorylation and dimerization. In a study involving breast cancer participants from India, the expression of prohibitin and its correlation with various clinico-pathological variables were found to be mainly significant. The same study also observed some point mutations in the breast cancer samples and mapped it to the exon 4 region.[29]

At first, PHB1 at Tyr-144 is phosphorylated by stimulation with insulin. This creates a binding site at SH2 domain which contains tyrosine phosphatase 1 (SHP1). It alters phosphorylation of Akt and glycogen synthase kinase-3β.[26],[62] Modifications by PHB1 associated with the significance of O-GlcNac are unclear. But, studies suggest that it is functionally relevant with phosphorylation at sites Tyr-114, Ser-121, Thr-258, and Tyr-259 in PHB1, which indicates its crucial role in PHB functions.[63],[64] Interestingly the exon 4 region of prohibitin contains the domain for binding retinoblastoma and E2F transcription factor.[26] These important findings indicate that prohibitin not only can be used as a biomarker but also holds potential in treating at least breast cancer. The mitochondrial inner membrane proteins OMA1 zinc metallopeptidase (OMA1) and optic atrophy-1 (OPA1) are regulated by tumor proteins p53 and prohibitins, PHB1 and PHB2 with reference to neoplastic diseases. Cancer cells rely on OMA1 and OPA1 for survival and thus confer resistance to chemotherapy.[65] In case of prostrate cancer, prohibitin along with heat shock protein 27 (HSP27) and aldehyde dehydrogenase 6A1 (ALDH6A1) acts as a tribiomarker. The trio predicts late metastatic prostate cancer.[66]

Rocaglamide is a natural anticancer drug which is shown to be directly bound to PHB1 and PHB2 and further inhibits the CRaf-MEK-ERK pathway and cancer cell proliferation. The knockdown of PHB mimics the role of rocaglamides on CRaf-MEK-ERK pathway and cell-cycle regulation. MEK/ERK pathway is the important pathway that regulates the chain of protein synthesis, which is involved in tumor cell survival and cancer progression; PHB here shows to have potential as molecular target for cancer chemotherapy.[67]

  Prohibitin Role in Other Diseases Top

Prohibitin is found inside the mitochondria of cells, and mitochondria are responsible for providing energy for almost every biochemical and physiological reaction in our body. Mutations in PHB can induce not only cancer, but also many other diseases such as PD, AD, and diseases associated with kidney and heart [Figure 2]. Prohibitin has been linked to adipocyte as the overexpressing of prohibitin promoted adipogenesis and its knockdown resulted in enervated adipogenesis.[68],[69] In Saccharomyces cerevisiae, the disruption of prohibitin caused much decrease in the lifespan (replicative) and also resulted in the morphological change in the cells, which is a peculiar feature of aging.[70] Previous studies related to PD and AD stated that loss of PHB can deteriorate the function of neurons.[21] In addition to this, overexpression of PHB has been found to induce resistance to apoptosis and provides more susceptibility to apoptosis in case of less production of PHB. It has also been found that PHB is related to the modulation of the ATP Synthase complex[71] due to mitochondrial dysfunction.[21] Evidence shows that transglutaminase serves as the substrate for prohibitin which might help in the pathogenesis of sporadic AD, Huntington’s disease, and other neurological diseases.[21],[72]
Figure 2: Interaction of PHB gene with diseases. Mutations in PHB show various effects not only on cancer but on other diseases as well

Click here to view

Prohibitin being a part of molecular pathways has its significance in diseases associated to heart and kidneys as well. PHB serves as a target molecule in cardio-vascular screening and can be used as a therapeutic approach toward the same.[73] In renal diseases, the mitochondrial network associated with glomerular cells regulates the function of nephrons in ultrafiltration of urine. In a mouse model, podocyte-specific PHB-2 knockout has been observed to cause glomerulosclerosis, renal failure, and death within 4–5 days.[54],[21],[74] The interaction of prohibitin with diseases is shown in [Figure 2].

  Conclusion Top

The role of prohibitin in cancer development is not new but recent studies have noticed the activity of prohibitin in a more meaningful way. In some cases, prohibitin is known to contribute to the development or progression of cancer, whereas major studies have pointed out its activity in inhibition of cancer cells. Overall, prohibitin’s function in tumor suppression holds much more potential when compared with contradictory studies that place the gene in the pro-tumorigenic category. The protein expression analysis has also uncovered the fact that prohibitin can be used as a potential biomarker in the prognosis of cancer. Interestingly, the presence of crucial binding sites for the tumor suppressive genes such as retinoblastoma (Rb), p53, and E2F on the prohibitin’s domain exhibits the therapeutic value in terms of treatment and disease management.

Financial support and sponsorship

The grant for this project was provided by the Department of Science and Technology (DST) (Grant No.: SR/WOS-A/LS-525/2016), Government of India, New Delhi, India.

Conflicts of interest

The authors declare that there is no conflict of interest.

  References Top

Bavelloni A, Piazzi M, Raffini M, Faenza I, Blalock WL. Prohibitin 2: At a communications crossroads. IUBMB Life 2015;67:239-54.  Back to cited text no. 1
Sato T, Sakamoto T, Takita K, Saito H, Okui K, Nakamura Y. The human prohibitin (PHB) gene family and its somatic mutations in human tumors. Genomics 1993;17:762-4, ISSN 0888-7543, https://doi.org/10.1006/geno.1993.1402  Back to cited text no. 2
Wang D, Tabti R, Elderwish S, Djehal A, Chouha N, Pinot F, et al. SFPH proteins as therapeutic targets for a myriad of diseases. Bioorg Med Chem Lett 2020;30:127600.  Back to cited text no. 3
Yokoyama H, Matsui I. The lipid raft markers stomatin, prohibitin, flotillin, and HflK/C (SPFH)-domain proteins form an operon with NfeD proteins and function with apolarpolyisoprenoid lipids. Crit Rev Microbiol 2020;46:38-48.  Back to cited text no. 4
Nijtmans LG, de Jong L, Artal Sanz M, Coates PJ, Berden JA, Back JW, et al. Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins. Embo J 2000;19:2444-51.  Back to cited text no. 5
Tatsuta T, Langer T. Quality control of mitochondria: Protection against neurodegeneration and ageing. Embo J 2008;27:306-14.  Back to cited text no. 6
Wintachai P, Wikan N, Kuadkitkan A, Jaimipuk T, Ubol S, Pulmanausahakul R, et al. Identification of prohibitin as a chikungunya virus receptor protein. J Med Virol 2012;84:1757-70.  Back to cited text no. 7
Desideri E, Cavallo AL, Baccarini M. Alike but different: RAF paralogs and their signaling outputs. Cell 2015;161:967-70.  Back to cited text no. 8
Yang J, Li B, He QY. Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment. Cell Death Dis 2018;9:580.  Back to cited text no. 9
Koushyar S, Economides G, Zaat S, Jiang W, Bevan CL, Dart DA. The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen signalling in prostate cancer cells. Oncogenesis 2017;6:e333.  Back to cited text no. 10
McClung JK, Jupe ER, Liu X-T, Dell’Orco RT. Prohibitin: Potential role in senescence, development, and tumor suppression. Exp Gerontol 1995;30:99-124, ISSN 0531-5565, https://doi.org/10.1016/0531-5565(94)00069-7  Back to cited text no. 11
Wang S, Nath N, Fusaro G, Chellappan S. Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals. Mol Cell Biol 1999;19:7447-60.  Back to cited text no. 12
Gamble S, Odontiadis M, Waxman J, Westbrook JA, Dunn MJ, Wait R, et al. Androgens target prohibitin to regulate proliferation of prostate cancer cells. Oncogene2004;23:2996-3004. https://doi.org/10.1038/sj.onc.1207444  Back to cited text no. 13
Liu P, Xu Y, Zhang W, Li Y, Tang L, Chen W, et al. Prohibitin promotes androgen receptor activation in ER-positive breast cancer. Cell Cycle 2017;16:776-84.  Back to cited text no. 14
Manjeshwar S, Branam DE, Lerner MR, Brackett DJ, Jupe ER. Tumor suppression by the prohibitin gene 3’untranslated region RNA in human breast cancer. Cancer Res 2003;63:5251-6.  Back to cited text no. 15
Jupe ER, Badgett AA, Neas BR, Craft MA, Mitchell DS, Resta R, et al. Single nucleotide polymorphism in prohibitin 3′untranslated region and breast-cancer susceptibility. Lancet 2001;357:1588-9. ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(00)04747-4  Back to cited text no. 16
Zhang B, Chambers KJ, Faller DV, Wang S. Reprogramming of the SWI/SNF complex for co-activation or co-repression in prohibitin-mediated estrogen receptor regulation. Oncogene 2007;26:7153-7.  Back to cited text no. 17
Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S. Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. J Biol Chem 2003;278:47853-61.  Back to cited text no. 18
Joshi B, Rastogi S, Morris M, Carastro LM, DeCook C, Seto E, et al. Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites. Biochem J 2007;401:155-66.  Back to cited text no. 19
Thuaud F, Ribeiro N, Nebigil CG, Désaubry L. Prohibitin ligands in cell death and survival: Mode of action and therapeutic potential. Chem Biol 2013;20:316-31.  Back to cited text no. 20
Signorile A, Sgaramella G, Bellomo F, De Rasmo D. Prohibitins: A critical role in mitochondrial functions and implication in diseases. Cells2019;8:71. doi: 10.3390/cells8010071  Back to cited text no. 21
Merkwirth C, Langer T. Prohibitin function within mitochondria: Essential roles for cell proliferation and cristae morphogenesis. Biochim Biophys Acta 2009;1793:27-32.  Back to cited text no. 22
Kasashima K, Ohta E, Kagawa Y, Endo H. Mitochondrial functions and estrogen receptor-dependent nuclear translocation of pleiotropic human prohibitin 2. J Biol Chem 2006;281:36401-10.  Back to cited text no. 23
Jiang L, Dong P, Zhang Z, Li C, Li Y, Liao Y, et al. Akt phosphorylates prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells. Cell Death Dis 2015;6:e1660.  Back to cited text no. 24
Zhou TB, Qin YH. Signaling pathways of prohibitin and its role in diseases. J Recept Signal Transduct Res 2013;33:28-36.  Back to cited text no. 25
Wang S, Nath N, Adlam M, Chellappan S. Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function. Oncogene 1999;18:3501-10.  Back to cited text no. 26
Sato T, Saito H, Swensen J, Olifant A, Wood C, Danner D, et al. The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer. Cancer Res 1992;52:1643-6.  Back to cited text no. 27
Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990;250:1684-9.  Back to cited text no. 28
Najm MZ, Zaidi S, Siddiqui WA, Husain SA. Immunohistochemical expression and mutation study of prohibitin gene in Indian female breast cancer cases. Med Oncol 2013;30:614.  Back to cited text no. 29
Franzoni A, Dima M, D’Agostino M, Puppin C, Fabbro D, Loreto CD, et al. Prohibitin is overexpressed in papillary thyroid carcinomas bearing the BRAF(V600E) mutation. Thyroid Off J Am Thyroid Assoc 2009;19:247-55.  Back to cited text no. 30
Ummanni R, Junker H, Zimmermann U, Venz S, Teller S, Giebel J, et al. Prohibitin identified by proteomic analysis of prostate biopsies distinguishes hyperplasia and cancer. Cancer Lett 2008;266:171-85.  Back to cited text no. 31
Wu TF, Wu H, Wang YW, Chang TY, Chan SH, Lin YP . Prohibitin in the pathogenesis of transitional cell bladder cancer. Anticancer Res 2007;27:895-900.  Back to cited text no. 32
Fraser M, Leung B, Jahani-Asl A, Yan X, Thompson WE, Tsang BK . Chemoresistance in human ovarian cancer: The role of apoptotic regulators. Reprod Biol Endocrinol 2003;1:66.  Back to cited text no. 33
Liu T, Tang H, Lang Y, Liu M, Li X . MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Lett 2009;273:2.  Back to cited text no. 34
Xu Z, Wu J, Zha X. Up-regulation of prohibitin 1 is involved in the proliferation and migration of liver cancer cells. Sci China Life Sci 2011;54:121-7.  Back to cited text no. 35
Coates PJ, Nenutil R, McGregor A, Picksley SM, Crouch DH, Hall PA, et al. Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. Exp Cell Res 2001;265:262-73.  Back to cited text no. 36
Ko KS, Tomasi ML, Iglesias-Ara A, French BA, French SW, Ramani K , et al. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice. Hepatology (Baltimore, MD) 2010;52:6.  Back to cited text no. 37
Du MD, He KY, Qin G, Chen J, Li JY . Adriamycin resistance-associated prohibitin gene inhibits proliferation of human osteosarcoma MG63 cells by interacting with oncogenes and tumor suppressor genes. Oncol Lett 2016;12:3.  Back to cited text no. 38
Liao Q, Guo X, Li X, Xiong W, Li X, Yang J, et al. Prohibitin is an important biomarker for nasopharyngeal carcinoma progression and prognosis. Eur J Cancer Prevent 2013;22:68-76.  Back to cited text no. 39
Feng F, Qiu B, Zang R, Song P, Gao S . Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression. Oncotarget 2017;8:29091-100.  Back to cited text no. 40
Cheng J, Gao F, Chen X, Wu J, Xing C, Lv Z, et al. Prohibitin-2 promotes hepatocellular carcinoma malignancy progression in hypoxia based on a label-free quantitative proteomics strategy. Mol Carcinogen 2014;53:820-32.  Back to cited text no. 41
Kim NH, Yoshimaru T, Chen YA, Matsuo T, Komatsu M, Miyoshi Y, et al. BIG3 inhibits the estrogen-dependent nuclear translocation of PHB2 via multiple karyopherin-alpha proteins in breast cancer cells. PLoS ONE 2015;10:e0127707.  Back to cited text no. 42
Jiang P, Xiang Y, Wang YJ, Li SM, Wang Y, Hua HR,et al. Differential expression and subcellular localization of prohibitin 1 are related to tumorigenesis and progression of non-small cell lung cancer. Int J Clin Exp Pathol 2013;6:2092-101.  Back to cited text no. 43
Theiss AL, Vijay-Kumar M, Obertone TS, Jones DP, Hansen JM, Gewirtz AT, et al. Prohibitin is a novel regulator of antioxidant response that attenuates colonic inflammation in mice. Gastroenterology 2009;137:199-208, 208.e1-6.  Back to cited text no. 44
Dart DA, Spencer-Dene B, Gamble SC, Waxman J, Bevan CL. Manipulating prohibitin levels provides evidence for an in vivo role in androgen regulation of prostate tumours. Endocr Relat Cancer 2009;16:1157-69.  Back to cited text no. 45
Kang X, Zhang L, Sun J, Ni Z, Ma Y, Chen X, et al. Prohibitin: A potential biomarker for tissue-based detection of gastric cancer. J Gastroenterol 2008;43:618-25.  Back to cited text no. 46
Ren HZ, Wang JS, Wang P, Pan GQ, Wen JF, Fu H, et al. Increased expression of prohibitin and its relationship with poor prognosis in esophageal squamous cell carcinoma. Pathol Oncol Res 2010;16:515-22.  Back to cited text no. 47
Chen D, Chen F, Lu X, Yang X, Xu Z, Pan J, et al. Identification of prohibitin as a potential biomarker for colorectal carcinoma based on proteomics technology. Int J Oncol 2010;37:355-65.  Back to cited text no. 48
Jupe ER, Liu XT, Kiehlbauch JL, McClung JK, Dell’Orco RT. Prohibitin in breast cancer cell lines: Loss of antiproliferative activity is linked to 3’ untranslated region mutations. Cell Growth Differ 1996;7:871-8.  Back to cited text no. 49
Cao Y, et al. Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer. J Exp Clin Cancer Res 2016;35:1-11.  Back to cited text no. 50
Liao Q, Guo X, Li X, Xiong W, Li X, Yang J, et al. Prohibitin is an important biomarker for nasopharyngeal carcinoma progression and prognosis. Eur J Cancer Prev 2013;22:68-76.  Back to cited text no. 51
Chumbalkar VC, Subhashini C, Dhople VM, Sundaram CS, Jagannadham MV, Kumar KN, et al. Differential protein expression in human gliomas and molecular insights. Proteomics 2005;5:1167-77.  Back to cited text no. 52
Durackova Z. Oxidants, antioxidants and oxidative stress. In: Gvozdjáková A, editor. Mitochondrial Medicine. Mitochondrial Metabolism, Diseases, Diagnosis and Therapy. Amsterdam: Springer;2008. pp. 19-49.  Back to cited text no. 53
Zhou T-B, Qin Y-H. Signaling pathways of prohibitin and its role in diseases. J Recept Signal Transduct Res 2013;33:28-36. doi:10.3109/10799893.2012.752006  Back to cited text no. 54
Henschke P, Vorum H, Honoré B, Rice GE. Protein profiling the effects of in vitro hyperoxic exposure on fetal rabbit lung. Proteomics 2006;6:1957-62.  Back to cited text no. 55
Aruoma OI, Neergheen VS, Bahorun T, Jen L-S. Free radicals, antioxidants and diabetes: Embryopathy, retinopathy, neuropathy, nephropathy and cardiovascular complications. Neuroembryol Aging 2007;4:117-37.  Back to cited text no. 56
Satheesh Kumar MK, Nair S, Mony U, Kalingavarman S, Venkat R, Sivanarayanan TB, et al. Significance of elevated prohibitin 1 levels in multiple sclerosis patients lymphocytes towards the assessment of subclinical disease activity and its role in the central nervous system pathology of disease. Int J Biol Macromol 2018;110:573-81.  Back to cited text no. 57
Muchová J. Diabetes mellitus and antioxidants. In: ďuračková Z, bergendi Ľ, čársky J, editors. Free Radicals and Antioxidants in Medicine (II) (in Slovak). Bratislava: SAP;1999. pp. 203-32.  Back to cited text no. 58
Cherubini A, Ruggiero C, Polidori MC, Mecocci P. Potential markers of oxidative stress in stroke. Free Radic Biol Med 2005;39:841-52.  Back to cited text no. 59
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006;160:1-40.  Back to cited text no. 60
Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxid Redox Signal 2008;10:1923-40.  Back to cited text no. 61
Nystrom FH, Quon MJ. Insulin signalling: Metabolic pathways and mechanisms for specificity. Cell Signal 1999;11:563-74.  Back to cited text no. 62
Ande SR, Moulik S, Mishra S. Interaction between O-glcnac modification and tyrosine phosphorylation of prohibitin: Implication for a novel binary switch. PLoS ONE 2009;4:e4586.  Back to cited text no. 63
Mishra S, Ande SR, Salter NW. O-glcnac modification: Why so intimately associated with phosphorylation? Cell Commun Signal 2011;9:1.  Back to cited text no. 64
Alavi MV. Targeted OMA1 therapies for cancer. Int J Cancer 2019;145:2330-41.  Back to cited text no. 65
Cho SY, Kang S, Kim DS, Na HJ, Kim YJ, Choi YD, et al. HSP27, ALDH6A1 and prohibitin act as a trio-biomarker to predict survival in late metastatic prostate cancer. Anticancer Res 2018;38:6551-60.  Back to cited text no. 66
Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, et al. The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2. Chem Biol 2012;19:1093-104.  Back to cited text no. 67
Ande SR, Xu Z, Gu Y, Mishra S. Prohibitin has an important role in adipocyte differentiation. Int J Obes (Lond) 2012;36:1236-44.  Back to cited text no. 68
Liu D, Lin Y, Kang T, Huang B, Xu W, Garcia-Barrio M, et al. Mitochondrial dysfunction and adipogenic reduction by prohibitin silencing in 3T3-L1 cells. PLoS One 2012;7:e34315.  Back to cited text no. 69
Coates PJ, Jamieson DJ, Smart K, Prescott AR, Hall PA. The prohibitin family of mitochondrial proteins regulate replicative lifespan. Curr Biol 1997;7:607-10.  Back to cited text no. 70
Dutta D, Ali N, Banerjee E, Singh R, Naskar A, Paidi RK, et al. Low levels of prohibitin in substantia nigra makes dopaminergic neurons vulnerable in Parkinson’s disease. Mol Neurobiol 2018;55:804-21.  Back to cited text no. 71
Battaglia G, Farrace MG, Mastroberardino PG, Viti I, Fimia GM, Van Beeumen J, et al. Transglutaminase 2 ablation leads to defective function of mitochondrial respiratory complex I affecting neuronal vulnerability in experimental models of extrapyramidal disorders. J Neurochem 2007;100:36-49.  Back to cited text no. 72
Chowdhury D, Kumar D, Sarma P, Tangutur AD, Bhadra MP. PHB in cardiovascular and other diseases: Present knowledge and implications. Curr Drug Targets 2017;18:1836-51.  Back to cited text no. 73
Ising C, Brinkkoetter PT. Prohibitin signaling at the kidney filtration barrier. Adv Exp Med Biol 2017;982:563-75. doi:10.1007/978-3-319-55330-6_29  Back to cited text no. 74


  [Figure 1], [Figure 2]

  [Table 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Prohibitin Gene
Localization of ...
Mutations in Pro...
Role of Prohibit...
Therapeutic Appl...
Prohibitin Role ...
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded77    
    Comments [Add]    

Recommend this journal