Skip to main content
Top
Published in: Archives of Gynecology and Obstetrics 5/2015

01-11-2015 | Gynecologic Oncology

miR-31 functions as an oncogene in cervical cancer

Authors: Wenjing Zheng, Zhen Liu, Wei Zhang, Xiaoxia Hu

Published in: Archives of Gynecology and Obstetrics | Issue 5/2015

Login to get access

Abstract

Background

MicroRNAs are frequently altered in numerous cancers and are critical regulators of various diseases. miR-31 has been shown to be significantly altered in a variety of cancers.

Methods

In the present study, we measured the expression level of miR-31 in cervical cancer, CIN and normal cervical tissues by real-time RT (reverse transcription)-PCR. We also analyzed the correlations between the expression level of miR-31 and the clinical characteristics in cases of cervical squamous cell carcinoma. In addition, we measured the expression of miR-31 in cervical cancer cell lines, and transfected HPV16 E6 siRNA and HPV16 E7 siRNA into SiHa cells to investigate the effects on miR-31. Finally, the effects of miR-31 on cell proliferation, migration and invasion were measured in HeLa and SiHa cells that were transfected with a miR-31 mimic or a negative control.

Result

We found that the expression level of miR-31 was significantly higher in cervical cancer patients than in normal individuals (P < 0.05). Aberrant expression of miR-31 was positively correlated with the lymph node metastasis (LNM), vessel invasion and HPV status (P < 0.05). Additionally, miR-31 was also overexpressed in the cervical cancer-derived HeLa and SiHa cells compared with C33A cells (P < 0.05). Moreover, a relationship was found between miR-31 expression and the HPV16 oncoproteins E6/E7. Furthermore, we found that the overexpression of miR-31 can promote cell proliferation and enhance the migration and invasion abilities of cancer cells.

Conclusions

Our results suggested that miR-31 plays an oncogenetic role in the development and progression of cervical cancer.
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMed
2.
go back to reference Shi TY, Chen XJ, Zhu ML, Wang MY, He J, Yu KD, Shao ZM, Sun MH, Zhou XY, Cheng X, Wu X, Wei Q (2013) A pri-miR-218 variant and risk of cervical carcinoma in Chinese women. BMC Cancer 13:19CrossRefPubMedCentralPubMed Shi TY, Chen XJ, Zhu ML, Wang MY, He J, Yu KD, Shao ZM, Sun MH, Zhou XY, Cheng X, Wu X, Wei Q (2013) A pri-miR-218 variant and risk of cervical carcinoma in Chinese women. BMC Cancer 13:19CrossRefPubMedCentralPubMed
3.
go back to reference Zhang J, Li S, Yan Q, Chen X, Yang Y, Liu X, Wan X (2013) Interferon-beta induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells. PLoS One 8:e81366CrossRefPubMedCentralPubMed Zhang J, Li S, Yan Q, Chen X, Yang Y, Liu X, Wan X (2013) Interferon-beta induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells. PLoS One 8:e81366CrossRefPubMedCentralPubMed
4.
go back to reference Wilting SM, Snijders PJ, Verlaat W, Jaspers A, van de Wiel MA, van Wieringen WN, Meijer GA, Kenter GG, Yi Y, le Sage C, Agami R, Meijer CJ, Steenbergen RD (2013) Altered microRNA expression associated with chromosomal changes contributes to cervical carcinogenesis. Oncogene 32:106–116CrossRefPubMed Wilting SM, Snijders PJ, Verlaat W, Jaspers A, van de Wiel MA, van Wieringen WN, Meijer GA, Kenter GG, Yi Y, le Sage C, Agami R, Meijer CJ, Steenbergen RD (2013) Altered microRNA expression associated with chromosomal changes contributes to cervical carcinogenesis. Oncogene 32:106–116CrossRefPubMed
5.
go back to reference Korner C, Keklikoglou I, Bender C, Worner A, Munstermann E, Wiemann S (2013) MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKC epsilon). J Biol Chem 288:8750–8761CrossRefPubMedCentralPubMed Korner C, Keklikoglou I, Bender C, Worner A, Munstermann E, Wiemann S (2013) MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKC epsilon). J Biol Chem 288:8750–8761CrossRefPubMedCentralPubMed
6.
go back to reference Wang N, Zhou Y, Zheng L, Li H (2014) MiR-31 is an independent prognostic factor and functions as an oncomir in cervical cancer via targeting ARID1A. Gynecol Oncol 134:129–137CrossRefPubMed Wang N, Zhou Y, Zheng L, Li H (2014) MiR-31 is an independent prognostic factor and functions as an oncomir in cervical cancer via targeting ARID1A. Gynecol Oncol 134:129–137CrossRefPubMed
7.
go back to reference Rao Q, Shen Q, Zhou H, Peng Y, Li J, Lin Z (2012) Aberrant microRNA expression in human cervical carcinomas. Med Oncol 29:1242–1248CrossRefPubMed Rao Q, Shen Q, Zhou H, Peng Y, Li J, Lin Z (2012) Aberrant microRNA expression in human cervical carcinomas. Med Oncol 29:1242–1248CrossRefPubMed
8.
go back to reference Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM (2008) Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 3:e2557CrossRefPubMedCentralPubMed Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM (2008) Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 3:e2557CrossRefPubMedCentralPubMed
10.
go back to reference Xu RS, Wu XD, Zhang SQ, Li CF, Yang L, Li DD, Zhang BG, Zhang Y, Jin JP, Zhang B (2013) The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer. Int J Oncol 42:676–682PubMed Xu RS, Wu XD, Zhang SQ, Li CF, Yang L, Li DD, Zhang BG, Zhang Y, Jin JP, Zhang B (2013) The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer. Int J Oncol 42:676–682PubMed
11.
go back to reference Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest 120:1298–1309CrossRefPubMedCentralPubMed Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest 120:1298–1309CrossRefPubMedCentralPubMed
12.
go back to reference Wang S, Li Q, Wang K, Dai Y, Yang J, Xue S, Han F, Zhang Q, Liu J, Wu W (2013) Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer. Clin Transl Oncol 15:849–854CrossRefPubMed Wang S, Li Q, Wang K, Dai Y, Yang J, Xue S, Han F, Zhang Q, Liu J, Wu W (2013) Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer. Clin Transl Oncol 15:849–854CrossRefPubMed
13.
go back to reference Cheung TH, Man KN, Yu MY, Yim SF, Siu NS, Lo KW, Doran G, Wong RR, Wang VW, Smith DI, Worley MJ, Berkowitz RS, Chung TK, Wong YF (2012) Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle 11:2876–2884CrossRefPubMed Cheung TH, Man KN, Yu MY, Yim SF, Siu NS, Lo KW, Doran G, Wong RR, Wang VW, Smith DI, Worley MJ, Berkowitz RS, Chung TK, Wong YF (2012) Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle 11:2876–2884CrossRefPubMed
14.
go back to reference Rahma OE, Herrin VE, Ibrahim RA, Toubaji A, Bernstein S, Dakheel O, Steinberg SM, Abu ER, Mkrtichyan M, Berzofsky JA, Khleif SN (2014) Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. J Transl Med 12:353CrossRefPubMedCentralPubMed Rahma OE, Herrin VE, Ibrahim RA, Toubaji A, Bernstein S, Dakheel O, Steinberg SM, Abu ER, Mkrtichyan M, Berzofsky JA, Khleif SN (2014) Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. J Transl Med 12:353CrossRefPubMedCentralPubMed
15.
go back to reference Nambaru L, Meenakumari B, Swaminathan R, Rajkumar T (2009) Prognostic significance of HPV physical status and integration sites in cervical cancer. Asian Pac J Cancer Prev 10:355–360PubMed Nambaru L, Meenakumari B, Swaminathan R, Rajkumar T (2009) Prognostic significance of HPV physical status and integration sites in cervical cancer. Asian Pac J Cancer Prev 10:355–360PubMed
16.
go back to reference Martinez I, Gardiner AS, Board KF, Monzon FA, Edwards RP, Khan SA (2008) Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene 27:2575–2582CrossRefPubMedCentralPubMed Martinez I, Gardiner AS, Board KF, Monzon FA, Edwards RP, Khan SA (2008) Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene 27:2575–2582CrossRefPubMedCentralPubMed
17.
go back to reference Xi Y, Shalgi R, Fodstad O, Pilpel Y, Ju J (2006) Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clin Cancer Res 12:2014–2024CrossRefPubMed Xi Y, Shalgi R, Fodstad O, Pilpel Y, Ju J (2006) Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clin Cancer Res 12:2014–2024CrossRefPubMed
18.
go back to reference Melar-New M, Laimins LA (2010) Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. J Virol 84:5212–5221CrossRefPubMedCentralPubMed Melar-New M, Laimins LA (2010) Human papillomaviruses modulate expression of microRNA 203 upon epithelial differentiation to control levels of p63 proteins. J Virol 84:5212–5221CrossRefPubMedCentralPubMed
19.
go back to reference Li B, Hu Y, Ye F, Li Y, Lv W, Xie X (2010) Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. Int J Gynecol Cancer 20:597–604CrossRefPubMed Li B, Hu Y, Ye F, Li Y, Lv W, Xie X (2010) Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. Int J Gynecol Cancer 20:597–604CrossRefPubMed
20.
go back to reference Au YC, Tsang TY, Yau PL, Kwok TT (2011) Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene 30:2401–2410CrossRef Au YC, Tsang TY, Yau PL, Kwok TT (2011) Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene 30:2401–2410CrossRef
21.
go back to reference Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, Kappeler A, Brunner T, Vassella E (2009) miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res 69:5553–5559CrossRefPubMed Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, Kappeler A, Brunner T, Vassella E (2009) miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res 69:5553–5559CrossRefPubMed
22.
go back to reference Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14:1271–1277CrossRefPubMed Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D’Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008) The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14:1271–1277CrossRefPubMed
23.
go back to reference Zhao S, Yao DS, Chen JY, Ding N (2013) Aberrant expression of miR-20a and miR-203 in cervical cancer. Asian Pac J Cancer Prev 14:2289–2293CrossRefPubMed Zhao S, Yao DS, Chen JY, Ding N (2013) Aberrant expression of miR-20a and miR-203 in cervical cancer. Asian Pac J Cancer Prev 14:2289–2293CrossRefPubMed
24.
go back to reference Chen J, Yao D, Zhao S, He C, Ding N, Li L, Long F (2014) MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2. Arch Gynecol Obstet 290:725–732CrossRefPubMed Chen J, Yao D, Zhao S, He C, Ding N, Li L, Long F (2014) MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2. Arch Gynecol Obstet 290:725–732CrossRefPubMed
25.
go back to reference Li JH, Xiao X, Zhang YN, Wang YM, Feng LM, Wu YM, Zhang YX (2011) MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol 120:145–151CrossRefPubMed Li JH, Xiao X, Zhang YN, Wang YM, Feng LM, Wu YM, Zhang YX (2011) MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol 120:145–151CrossRefPubMed
26.
go back to reference Yao T, Lin Z (2012) MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta 1822:248–260CrossRefPubMed Yao T, Lin Z (2012) MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta 1822:248–260CrossRefPubMed
27.
go back to reference Hu X, Schwarz JK, Lewis JJ, Huettner PC, Rader JS, Deasy JO, Grigsby PW, Wang X (2010) A microRNA expression signature for cervical cancer prognosis. Cancer Res 70:1441–1448CrossRefPubMedCentralPubMed Hu X, Schwarz JK, Lewis JJ, Huettner PC, Rader JS, Deasy JO, Grigsby PW, Wang X (2010) A microRNA expression signature for cervical cancer prognosis. Cancer Res 70:1441–1448CrossRefPubMedCentralPubMed
28.
go back to reference Zhang T, Wang Q, Zhao D, Cui Y, Cao B, Guo L, Lu SH (2011) The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma. Clin Sci (Lond) 121:437–447CrossRef Zhang T, Wang Q, Zhao D, Cui Y, Cao B, Guo L, Lu SH (2011) The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma. Clin Sci (Lond) 121:437–447CrossRef
29.
go back to reference Wang A, Landen NX, Meisgen F, Lohcharoenkal W, Stahle M, Sonkoly E, Pivarcsi A (2014) MicroRNA-31 is overexpressed in cutaneous squamous cell carcinoma and regulates cell motility and colony formation ability of tumor cells. PLoS One 9:e103206CrossRefPubMedCentralPubMed Wang A, Landen NX, Meisgen F, Lohcharoenkal W, Stahle M, Sonkoly E, Pivarcsi A (2014) MicroRNA-31 is overexpressed in cutaneous squamous cell carcinoma and regulates cell motility and colony formation ability of tumor cells. PLoS One 9:e103206CrossRefPubMedCentralPubMed
30.
go back to reference Hu C, Huang F, Deng G, Nie W, Huang W, Zeng X (2013) miR-31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Exp Ther Med 6:1265–1270PubMedCentralPubMed Hu C, Huang F, Deng G, Nie W, Huang W, Zeng X (2013) miR-31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Exp Ther Med 6:1265–1270PubMedCentralPubMed
31.
go back to reference Lei SL, Zhao H, Yao HL, Chen Y, Lei ZD, Liu KJ, Yang Q (2014) Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells. Oncol Lett 8:1768–1774PubMedCentralPubMed Lei SL, Zhao H, Yao HL, Chen Y, Lei ZD, Liu KJ, Yang Q (2014) Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells. Oncol Lett 8:1768–1774PubMedCentralPubMed
32.
go back to reference Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M, Stephens R, Simpson RM, Risinger JI, Jazaeri A, Niederhuber J (2010) The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle 9:4387–4398CrossRefPubMedCentralPubMed Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M, Stephens R, Simpson RM, Risinger JI, Jazaeri A, Niederhuber J (2010) The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle 9:4387–4398CrossRefPubMedCentralPubMed
33.
go back to reference Cottonham CL, Kaneko S, Xu L (2010) miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells. J Biol Chem 285:35293–35302CrossRefPubMedCentralPubMed Cottonham CL, Kaneko S, Xu L (2010) miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells. J Biol Chem 285:35293–35302CrossRefPubMedCentralPubMed
Metadata
Title
miR-31 functions as an oncogene in cervical cancer
Authors
Wenjing Zheng
Zhen Liu
Wei Zhang
Xiaoxia Hu
Publication date
01-11-2015
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 5/2015
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-015-3713-2

Other articles of this Issue 5/2015

Archives of Gynecology and Obstetrics 5/2015 Go to the issue