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Tumor Biology
Published in: Tumor Biology 9/2016

01-09-2016 | Original Article

MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway

Authors: Lili Song, Shikai Liu, Liang Zhang, Hairong Yao, Fangyuan Gao, Dongkui Xu, Qian Li

Published in: Tumor Biology | Issue 9/2016

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Abstract

MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression. MiR-21 overexpression decreases PTEN, increases p-Akt, and subsequently increases HIF-1α expression, while miR-21 inhibition results in increased PTEN, decreased p-Akt, and then decreased HIF-1α. Therefore, we inferred that there is a HIF-1α-miR-21 positive feedback loop through the PTEN/Akt/HIF-1α pathway in cervical cancer cells. In addition, we also demonstrated that miR-21 confers decreased autophagy in cervical cancer cells after IR via the Akt-mTOR signaling pathway. Decreased autophagy is one of the potential mechanisms of increased radioresistance in cervical cancer cells. These findings expand our understanding of radioresistance development in cervical cancer.
Literature
1.
2.
Ariga T, Toita T, Kasuya G, Nagai Y, Inamine M, Kudaka W, et al. External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer. J Radiat Res. 2013;54:690–6.CrossRefPubMedPubMedCentral
3.
Rogers L, Siu SS, Luesley D, Bryant A, Dickinson HO. Radiotherapy and chemoradiation after surgery for early cervical cancer. Cochrane Database Syst Rev. 2012;5:CD007583.PubMedCentral
4.
5.
6.
Liu S, Song L, Zhang L, Zeng S, Gao F. Mir-21 modulates resistance of hr-hpv positive cervical cancer cells to radiation through targeting lats1. Biochem Biophys Res Commun. 2015;459:679–85.CrossRefPubMed
7.
Shishodia G, Verma G, Srivastava Y, Mehrotra R, Das BC, Bharti AC. Deregulation of microRNAs let-7a and mir-21 mediate aberrant stat3 signaling during human papillomavirus-induced cervical carcinogenesis: role of e6 oncoprotein. BMC Cancer. 2014;14:996.CrossRefPubMedPubMedCentral
8.
Zhang J, Zhang C, Hu L, He Y, Shi Z, Tang S, et al. Abnormal expression of mir-21 and mir-95 in cancer stem-like cells is associated with radioresistance of lung cancer. Cancer Investig. 2015;33:165–71.CrossRef
9.
Liu J, Zhu H, Yang X, Ge Y, Zhang C, Qin Q, et al. MicroRNA-21 is a novel promising target in cancer radiation therapy. Tumour Biol. 2014;35:3975–9.CrossRefPubMed
10.
Fu Z, Chen D, Cheng H, Wang F. Hypoxia-inducible factor-1alpha protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia. Med Sci Monit. 2015;21:318–25.CrossRefPubMedPubMedCentral
11.
Liu J, Zhang J, Wang X, Li Y, Chen Y, Li K, et al. HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells. Exp Cell Res. 2010;316:1985–93.CrossRefPubMed
12.
Song Z, Ren H, Gao S, Zhao X, Zhang H, Hao J. The clinical significance and regulation mechanism of hypoxia-inducible factor-1 and mir-191 expression in pancreatic cancer. Tumour Biol. 2014;35:11319–28.CrossRefPubMed
13.
Xue M, Li X, Li Z, Chen W. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 2014;35:6901–12.CrossRefPubMed
14.
Yang Y, Yang Y, Yang X, Zhu H, Guo Q, Chen X, et al. Autophagy and its function in radiosensitivity. Tumour Biol. 2015;36:4079–87.CrossRefPubMed
15.
Koh WJ, Greer BE, Abu-Rustum NR, Apte SM, Campos SM, Cho KR, et al. Cervical cancer, version 2.2015. J Natl Compr Cancer Netw. 2015;13:395–404. quiz 404.
16.
Liu Y, Nie H, Zhang K, Ma D, Yang G, Zheng Z, et al. A feedback regulatory loop between HIF-1α and mir-21 in response to hypoxia in cardiomyocytes. FEBS Lett. 2014;588:3137–46.CrossRefPubMed
17.
Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, et al. MiR-21 induced angiogenesis through akt and erk activation and HIF-1α expression. PLoS One. 2011;6:e19139.CrossRefPubMedPubMedCentral
18.
Han M, Wang Y, Liu M, Bi X, Bao J, Zeng N, et al. MiR-21 regulates epithelial-mesenchymal transition phenotype and hypoxia-inducible factor-1α expression in third-sphere forming breast cancer stem cell-like cells. Cancer Sci. 2012;103:1058–64.CrossRefPubMed
19.
Luo H, Yang Y, Duan J, Wu P, Jiang Q, Xu C. PTEN-regulated akt/foxo3a/bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells. Cell Death Dis. 2013;4:e481.CrossRefPubMedPubMedCentral
20.
Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, et al. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000;60:1541–5.PubMed
21.
Miyazaki M, Miyazaki K, Chen S, Chandra V, Wagatsuma K, Agata Y, et al. The E-id protein axis modulates the activities of the PI3K-AKT-mTORC1-hif1a and c-myc/p19arf pathways to suppress innate variant TFH cell development, thymocyte expansion, and lymphomagenesis. Genes Dev. 2015;29:409–25.CrossRefPubMedPubMedCentral
22.
Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T, Mori S, et al. Targeting of tumor endothelial cells combining 2 gy/day of x-ray with everolimus is the effective modality for overcoming clinically relevant radioresistant tumors. Cancer Med. 2014;3:310–21.CrossRefPubMedPubMedCentral
23.
Martina JA, Chen Y, Gucek M, Puertollano R. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy. 2012;8:903–14.CrossRefPubMedPubMedCentral
24.
Yao T, Lin Z. Mir-21 is involved in cervical squamous cell tumorigenesis and regulates ccl20. Biochim Biophys Acta. 1822;2012:248–60.
25.
Hermansen SK, Nielsen BS, Aaberg-Jessen C, Kristensen BW. Mir-21 is linked to glioma angiogenesis: a co-localization study. J Histochem Cytochem. 2016;64:138–48.CrossRefPubMed
26.
Richart A, Loyer X, Neri T, Howangyin K, Guerin CL, Ngkelo A, et al. Microrna-21 coordinates human multipotent cardiovascular progenitors therapeutic potential. Stem Cells. 2014;32:2908–22.CrossRefPubMed
27.
Yang X, Cheng Y, Li P, Tao J, Deng X, Zhang X, et al. A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis. Tumour Biol. 2015;36:383–91.CrossRefPubMed
28.
Gwak HS, Kim TH, Jo GH, Kim YJ, Kwak HJ, Kim JH, et al. Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PLoS One. 2012;7:e47449.CrossRefPubMedPubMedCentral
29.
He C, Dong X, Zhai B, Jiang X, Dong D, Li B, et al. Mir-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/AKT pathway. Oncotarget. 2015;6:28867–81.PubMedPubMedCentral
30.
Sun Q, Liu T, Yuan Y, Guo Z, Xie G, Du S, et al. Mir-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting ubqln1. Int J Cancer. 2015;136:1003–12.CrossRefPubMed
31.
Liu Z, Huang S. Inhibition of mir-191 contributes to radiation-resistance of two lung cancer cell lines by altering autophagy activity. Cancer Cell Int. 2015;15:16.CrossRefPubMedPubMedCentral
Metadata
Title
MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway
Authors
Lili Song
Shikai Liu
Liang Zhang
Hairong Yao
Fangyuan Gao
Dongkui Xu
Qian Li
Publication date
01-09-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5073-3

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