nach oben

Tumor Biology

Erschienen in:

30.01.2016 | Original Article

MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis

verfasst von: Feiran Wang, Yong Qiang, Lirong Zhu, Yasu Jiang, Yinda Wang, Xian Shao, Lei Yin, Jiahui Chen, Zhong Chen

Erschienen in: Tumor Biology | Ausgabe 8/2016

Einloggen, um Zugang zu erhalten

Abstract

Recent studies have been shown that voltage-dependent anion channel 1 (VDAC1) plays an important role in carcinogenesis. However, its molecular biological function in hepatocellular carcinoma (HCC) has not been entirely clarified. This study investigated the expression of VDAC1 in HCC and its prognostic value for HCC patients. Furthermore, we also identify the relevant VDAC1 direct target. Western blot, real-time quantitative PCR (qRT-PCR), and immunohistochemical (IHC) staining were performed to detect the expression of VDAC1 in HCC. Furthermore, the relationship between the VDAC1 level and clinicopathological features and prognostic values was explored. The effects of VDAC1 on HCC cell proliferation, migration, and invasion were also investigated in vitro. Predicted target gene of VDAC1 was determined by dual-luciferase reporter assay, qRT-PCR, and Western blot analyses. Our results revealed elevated VDAC1 messenger RNA (mRNA) (P = 0.0020) and protein (P = 0.0035) expression in tumor tissue samples compared with paired adjacent non-tumorous tissue samples. High VDAC1 expression was correlated with distant metastasis (P = 0.025), differentiation (P = 0.002), and advanced tumor stage (P = 0.004) in HCC patients. Kaplan-Meier survival analysis demonstrated that high expression of VDAC1 was significantly correlated with a poor prognosis for HCC patients (P < 0.001). The multivariate analysis revealed that VDAC1 expression was an independent prognostic factor of the overall survival rate of HCC patients. Furthermore, knockdown of VDAC1 inhibits HCC cell proliferation, migration, and invasion in vitro. Moreover, further study revealed that miR-7 was a putative target of VDAC1. Our study suggested that miR-7 suppressed the expression of VDAC1. VDAC1 plays an important role in tumor progression and may be used as a potential role in the prognosis of HCC patients.

Roberts LR. Sorafenib in liver cancer—just the beginning. N Engl J Med. 2008;359:420–2.CrossRefPubMed

Olsen SK, Brown RS, Siegel AB. Hepatocellular carcinoma: review of current treatment with a focus on targeted molecular therapies. Therap Adv Gastroenterol. 2010;3:55–66.CrossRefPubMedPubMedCentral

El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.CrossRefPubMed

Benz R. Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins. Biochim Biophys Acta Rev Biomembr. 1994;1197:167–96.CrossRef

Hiller S, Abramson J, Mannella C, Wagner G, Zeth K. The 3D structures of VDAC represent a native conformation. Trends Biochem Sci. 2010;35:514–21.CrossRefPubMedPubMedCentral

Fiek C, Benz R, Roos N, Brdiczka D. Evidence for identity between the hexokinase-binding protein and the mitochondrial porin in the outer membrane of rat liver mitochondria. Biochimica Et Biophysica Acta. 1982;688:429–40.CrossRefPubMed

Shimizu S, Narita M, Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 1999;399:483–7.CrossRefPubMed

Shoshan-Barmatz V, De Pinto V, Zweckstetter M, Raviv Z, Keinan N, Arbel N. VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol Aspects Med. 2010;31:227–85.CrossRefPubMed

Shoshan-Barmatz V, Ben-Hail D. VDAC, a multi-functional mitochondrial protein as a pharmacological target. Mitochondrion. 2012;12:24–34.CrossRefPubMed

10.

Koren I, Raviv ZBV. Downregulation of voltage-dependent anion channel-1 expression by RNA interference prevents cancer cell growth in vivo. Cancer Biol Ther. 2010;9:1046–52.CrossRefPubMed

11.

Eriko S, Kei-Ichi H, Hiroki S, Junko K, Yukie N, Shigeomi S. Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel. Cancer Biol Ther. 2006;5:1523–9.CrossRef

12.

Claire G, Jithesh PV, Jaine B, Shu-Dong Z, Fennell DA. Gene expression meta-analysis identifies VDAC1 as a predictor of poor outcome in early stage non-small cell lung cancer. PLoS One. 2011;6:79–89.

13.

Nan J, Kham SKY, Koh GS, Lim JYS, Ariffin H, Chew FT, et al. Identification of prognostic protein biomarkers in childhood acute lymphoblastic leukemia (ALL). J Proteome. 2011;74:843–57.CrossRef

14.

Li M, Xiao ZQ, Chen ZC, Li JL, Li C, Zhang PF, et al. Proteomic analysis of the aging-related proteins in human normal colon epithelial tissue. J Biochem Mol Biol. 2007;40:72–81.PubMed

15.

Animals, humans, neoplasms, oncogenes: oncogenes meet metabolism. From deregulated genes to a broader understanding of tumour physiology. Preface. Ernst Schering Found Symp Proc 2007.

16.

Blachly-Dyson E, Forte M. VDAC channels. IUBMB Life. 2001;52:113–8.CrossRefPubMed

17.

Fulda S. Tumor resistance to apoptosis. Int J Cancer. 2009;124:511–5.CrossRefPubMed

18.

Brahimi-Horn MC, Mazure NM. Hypoxic VDAC1: a potential mitochondrial marker for cancer therapy. Adv Exp Med Biol. 2014;772:101–10.CrossRefPubMed

19.

Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4:891–9.CrossRefPubMed

20.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.CrossRefPubMed

21.

Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11:325–37.CrossRefPubMed

22.

Shoshan-Barmatz V, Golan M. Mitochondrial VDAC1: function in cell life and death and a target for cancer therapy. Curr Med Chem. 2012;19:714–35.CrossRefPubMed

23.

Ko JH, Gu W, Lim I, Zhou T, Bang H. Expression profiling of mitochondrial voltage-dependent anion channel-1 associated genes predicts recurrence-free survival in human carcinomas. PLoS One. 2014;9:e110094.CrossRefPubMedPubMedCentral

24.

Campbell AM, Chan SH. Mitochondrial membrane cholesterol, the voltage dependent anion channel (VDAC), and the Warburg effect. J Bioenerg Biomembr. 2008;40:193–7.CrossRefPubMed

25.

Arif T, Vasilkovsky L, Refaely Y, Konson A, Shoshan-Barmatz V. Silencing VDAC1 expression by siRNA inhibits cancer cell proliferation and tumor growth in vivo. Mol Ther Nucleic Acids. 2014;3:e159.CrossRefPubMedPubMedCentral

26.

Abu-Hamad S, Sivan S, Shoshan-Barmatz V. The expression level of the voltage-dependent anion channel controls life and death of the cell. Proc Natl Acad Sci U S A. 2006;103:5787–92.CrossRefPubMedPubMedCentral

27.

Shoshan-Barmatz V, Mizrachi D. VDAC1: from structure to cancer therapy. Front Oncol. 2012;2:164.CrossRefPubMedPubMedCentral

28.

Skalsky RL, Br. C: Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene. Plos One 2011;6:46–46.

29.

Foekens JA, Sieuwerts AM, Marcel S, Look MP, Vanja DW, Boersma AWM, et al. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A. 2008;105:13021–6.CrossRefPubMedPubMedCentral

30.

Veerla S, Lindgren DA, Frigyesi A, Staaf J, Persson H, Liedberg F, et al. MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer. 2009;124:2236–42.CrossRefPubMed

31.

Kong D, Piao YS, Yamashita S, Oshima H, Oguma K, Fushida S, et al. Inflammation-induced repression of tumor suppressor miR-7 in gastric tumor cells. Oncogene. 2012;31:3949–60.CrossRefPubMed

32.

Ikeda Y, Tanji E, Makino N, Kawata S, Furukawa T. MicroRNAs associated with mitogen-activated protein kinase in human pancreatic cancer. Mol Cancer Res. 2012;10:259–69.CrossRefPubMed

33.

Cheng AM, Byrom MW, Jeffrey S, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005;33:1290–7.CrossRefPubMedPubMedCentral

34.

Junn E, Lee KW, Jeong BS, Chan TW, Im JY, Mouradian MM. Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci U S A. 2009;106:13052–7.CrossRefPubMedPubMedCentral

35.

Zhang N, Li X, Wu CW, Dong Y, Cai M, Mok MTS, et al. MicroRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis. Oncogene. 2012;32:5078–88.CrossRefPubMed

36.

Ma C, Qi Y, Shao L, Liu M, Li X, Tang H. Downregulation of miR-7 upregulates Cullin 5 (CUL5) to facilitate G1/S transition in human hepatocellular carcinoma cells. IUBMB Life. 2013;65:1026–34.CrossRefPubMed

37.

Yu-Ting C, Hua-Heng L, Yung-Chang L, Yuan-Hung W, Chun-Fu H, Yu-Rung K, et al. EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF. Cancer Res. 2010;70:8822–31.CrossRef

38.

Yu Z, Ni L, Chen D, Zhang Q, Su Z, Wang Y, et al. Identification of miR-7 as an oncogene in renal cell carcinoma. J Mol Histol. 2013;44:669–77.CrossRefPubMed

39.

Saydam O, Senol O, Wurdinger T, Mizrak A, Ozdener GB, Stemmer-Rachamimov AO, et al. miRNA-7 attenuation in schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways. Cancer Res. 2011;71:852–61.CrossRefPubMed

Titel: MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis
verfasst von: Feiran Wang
Yong Qiang
Lirong Zhu
Yasu Jiang
Yinda Wang
Xian Shao
Lei Yin
Jiahui Chen
Zhong Chen
Publikationsdatum: 30.01.2016
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 8/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-4836-1

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis

Abstract

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2016

Transforming growth factor (TGF) β1 acted through miR-130b to increase integrin α5 to promote migration of colorectal cancer cells

Association of toll-like receptor 2 ∆22 and risk for gastric cancer considering main effects and interactions with smoking: a matched case-control study from Mizoram, India

The effect of antisense inhibitor of miRNA 106b∼25 on the proliferation, invasion, migration, and apoptosis of gastric cancer cell

The prognostic implication of SRSF2 mutations in Chinese patients with acute myeloid leukemia

Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status

ΔNp63α attenuates tumor aggressiveness by suppressing miR-205/ZEB1-mediated epithelial–mesenchymal transition in cervical squamous cell carcinoma

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie