Inhibition of miR‑21 promotes cell apoptosis in oral squamous cell carcinoma by upregulating PTEN

Zheng,Yanliang; Xie,Jingfang; Jiang,Fangfang; Li,Yunyun; Chang,Guanlin; Ma,Haiqing

doi:10.3892/or.2018.6663

Inhibition of miR‑21 promotes cell apoptosis in oral squamous cell carcinoma by upregulating PTEN

Authors:
- Yanliang Zheng
- Jingfang Xie
- Fangfang Jiang
- Yunyun Li
- Guanlin Chang
- Haiqing Ma
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Affiliations: Department of Stomatology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
Published online on: August 21, 2018 https://doi.org/10.3892/or.2018.6663
Pages: 2798-2805

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Abstract

MicroRNA‑21 (miR‑21) has been identified as an oncogene and confirmed to serve an important role in carcinogenesis in various types of cancer. However, the effect and mechanism of miR‑21 in oral squamous cell carcinoma (OSCC) has not been fully elucidated. In the present study, miR‑21 inhibitor and empty vector were transfected into OSCC cells, and non‑transfected cells were used as a blank control. The results indicated that when compared with the control and scramble groups, miR‑21 inhibitor suppressed the expression of miR‑21. Conversely, phosphatase and tensin homolog deletion on chromosome 10 (PTEN) was markedly upregulated, and a dual luciferase reporter assay revealed PTEN to be a target gene of miR‑21. Furthermore, miR‑21 inhibitor decreased the proliferation and invasion and enhanced the apoptosis of OSCC cells. There was no significant difference in cell proliferation, invasion and apoptosis between the control and scramble groups. The present data suggested that there may be a regulatory loop between miR‑21 and PTEN, and that miR‑21 inhibition affected the proliferative, invasive and apoptotic abilities of OSCC cells. These findings indicate that miR‑21 may be a possible novel target in the treatment of OSCC.

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1	Shi Z, Li Y, Qian X, Hu Y, Liu J, Zhang S and Zhang J: MiR-340 inhibits triple-negative breast cancer progression by reversing EZH2 mediated miRNAs dysregulated expressions. J Cancer. 8:3037–3048. 2017. View Article : Google Scholar : PubMed/NCBI
2	Hawa Z, Haque I, Ghosh A, Banerjee S, Harris L and Banerjee SK: The miRacle in pancreatic cancer by miRNAs: Tiny angels or devils in disease progression. Int J Mol Sci. 17:E8092016. View Article : Google Scholar : PubMed/NCBI
3	Zhang M, Matyunina LV, Walker LD, Chen W, Xiao H, Benigno BB, Wu R and McDonald JF: Evidence for the importance of post-transcriptional regulatory changes in ovarian cancer progression and the contribution of miRNAs. Sci Rep. 7:81712017. View Article : Google Scholar : PubMed/NCBI
4	Pereira CM, Sehnem D, da Fonseca EO, Barboza HFG, de Carvalho ACP, DaSilva AFM, Moura-Neto V and DosSantos MF: miRNAs: Important targets for oral cancer pain research. Biomed Res Int. 2017:40435162017. View Article : Google Scholar : PubMed/NCBI
5	Li L, Wang X, Li W, Yang L, Liu R, Zeng R, Wu Y and Shou T: miR-21 modulates prostaglandin signaling and promotes gastric tumorigenesis by targeting 15-PGDH. Biochem Biophys Res Commun. 495:928–934. 2018. View Article : Google Scholar : PubMed/NCBI
6	Yang Q, Xu E, Dai J, Wu J, Zhang S, Peng B and Jiang Y: miR-21 regulates N-methyl-N-nitro-N'-nitrosoguanidine-induced gastric tumorigenesis by targeting FASLG and BTG2. Toxicol Lett. 228:147–156. 2014. View Article : Google Scholar : PubMed/NCBI
7	Zhou B, Wang J, Zheng G and Qiu Z: Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21. Food Chem Toxicol. 97:375–384. 2016. View Article : Google Scholar : PubMed/NCBI
8	Wang P, Guan Q, Zhou D, Yu Z, Song Y and Qiu W: miR-21 inhibitors modulate biological functions of gastric cancer cells via PTEN/PI3K/mTOR pathway. DNA Cell Biol. 37:38–45. 2018. View Article : Google Scholar : PubMed/NCBI
9	Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A and Lund AH: Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 283:1026–1033. 2008. View Article : Google Scholar : PubMed/NCBI
10	Zhou S, Zhang S, Wang Y, Yi S, Zhao L, Tang X, Yu B, Gu X and Ding F: MiR-21 and miR-222 inhibit apoptosis of adult dorsal root ganglion neurons by repressing TIMP3 following sciatic nerve injury. Neurosci Lett. 586:43–49. 2015. View Article : Google Scholar : PubMed/NCBI
11	Ferraro A, Kontos CK, Boni T, Bantounas I, Siakouli D, Kosmidou V, Vlassi M, Spyridakis Y, Tsipras I, Zografos G, et al: Epigenetic regulation of miR-21 in colorectal cancer: ITGB4 as a novel miR-21 target and a three-gene network (miR-21-ITGBeta4-PDCD4) as predictor of metastatic tumor potential. Epigenetics. 9:129–141. 2014. View Article : Google Scholar : PubMed/NCBI
12	Chanyshev MD, Ushakov DS and Gulyaeva LF: Expression of miR-21 and its Acat1, Armcx1, and PTEN target genes in liver of female rats treated with DDT and benzo[a]pyrene. Mol Biol. 51:664–670. 2017.(In Russian). View Article : Google Scholar
13	Guo Y, Chang H, Li J, Xu XY, Shen L, Yu ZB and Liu WC: Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway. Apoptosis. 20:1109–1121. 2015. View Article : Google Scholar : PubMed/NCBI
14	Li XT, Wang HZ, Wu ZW, Yang TQ, Zhao ZH, Chen GL, Xie XS, Li B, Wei YX, Huang YL, et al: miR-494-3p regulates cellular proliferation, invasion, migration, and apoptosis by PTEN/AKT signaling in human glioblastoma cells. Cell Mol Neurobiol. 35:679–687. 2015. View Article : Google Scholar : PubMed/NCBI
15	Li Y, Sun J, Cai Y, Jiang Y, Wang X, Huang X, Yin Y and Li H: MiR-200a acts as an oncogene in colorectal carcinoma by targeting PTEN. Exp Mol Pathol. 101:308–313. 2016. View Article : Google Scholar : PubMed/NCBI
16	Gao ZQ, Wang JF, Chen DH, Ma XS, Wu Y, Tang Z and Dang XW: Long non-coding RNA GAS5 suppresses pancreatic cancer metastasis through modulating miR-32-5p/PTEN axis. Cell Biosci. 7:662017. View Article : Google Scholar : PubMed/NCBI
17	Sushma PS, Jamil K, Kumar PU, Satyanarayana U, Ramakrishna M and Triveni B: PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): A study on south Indian population. Tumour Biol. 37:7625–7632. 2016. View Article : Google Scholar : PubMed/NCBI
18	Nan Y, Guo L, Song Y, Wang L, Yu K, Huang Q and Zhong Y: Combinatorial therapy with adenoviral-mediated PTEN and a PI3K inhibitor suppresses malignant glioma cell growth in vitro and in vivo by regulating the PI3K/AKT signaling pathway. J Cancer Res Clin Oncol. 143:1477–1487. 2017. View Article : Google Scholar : PubMed/NCBI
19	Zhu X, Li Z, Li T, Long F, Lv Y, Liu L, Liu X and Zhan Q: Osthole inhibits the PI3K/AKT signaling pathway via activation of PTEN and induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma. Biomed Pharmacother. 102:502–509. 2018. View Article : Google Scholar : PubMed/NCBI
20	Chen X, Huang Z and Chen R: Microrna-136 promotes proliferation and invasion ingastric cancer cells through Pten/Akt/P-Akt signaling pathway. Oncol Lett. 15:4683–4689. 2018.PubMed/NCBI
21	Geletina NS, Kobelev VS, Babayants EV, Feng L, Pustylnyak VO and Gulyaeva LF: PTEN negative correlates with miR-181a in tumour tissues of non-obese endometrial cancer patients. Gene. 655:20–24. 2018. View Article : Google Scholar : PubMed/NCBI
22	Li B, Lu Y, Yu L, Han X, Wang H, Mao J, Shen J, Wang B, Tang J, Li C and Song B: miR-221/222 promote cancer stem-like cell properties and tumor growth of breast cancer via targeting PTEN and sustained Akt/NF-κB/COX-2 activation. Chem Biol Interact. 277:33–42. 2017. View Article : Google Scholar : PubMed/NCBI
23	Taghavi N and Yazdi I: Prognostic factors of survival rate in oral squamous cell carcinoma: Clinical, histologic, genetic and molecular concepts. Arch Iran Med. 18:314–319. 2015.PubMed/NCBI
24	Tamaki S, Kawakami M, Ishitani A, Kawashima W, Kasuda S, Yamanaka Y, Shimomura H, Imai Y, Nakagawa Y, Hatake K, et al: Soluble MICB serum levels correlate with disease stage and survival rate in patients with oral squamous cell carcinoma. Anticancer Res. 30:4097–4101. 2010.PubMed/NCBI
25	Li J, Huang H, Sun L, Yang M, Pan C, Chen W, Wu D, Lin Z, Zeng C, Yao Y, et al: MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res. 15:3998–4008. 2009. View Article : Google Scholar : PubMed/NCBI
26	Koenig AB, Barajas JM, Guerrero MJ and Ghoshal K: A comprehensive analysis of argonaute-clip data identifies novel, conserved and species-specific targets of mir-21 in human liver and hepatocellular carcinoma. Int J Mol Sci. 19:E8512018. View Article : Google Scholar : PubMed/NCBI
27	Yan F, Wang C, Li T, Cai W and Sun J: Role of miR-21 in the growth and metastasis of human salivary adenoid cystic carcinoma. Mol Med Rep. 17:4237–4244. 2018.PubMed/NCBI
28	Wu Y, Song Y, Xiong Y, Wang X, Xu K, Han B, Bai Y, Li L, Zhang Y and Zhou L: MicroRNA-21 (Mir-21) promotes cell growth and invasion by repressing tumor suppressor PTEN in colorectal cancer. Cell Physiol Biochem. 43:945–958. 2017. View Article : Google Scholar : PubMed/NCBI
29	Jung S, Li C, Jeong D, Lee S, Ohk J, Park M, Han S, Duan J, Kim C, Yang Y, et al: Oncogenic function of p34^SEI-1 via NEDD41 mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway. Int J Oncol. 43:1587–1595. 2013. View Article : Google Scholar : PubMed/NCBI
30	Wang L, Tang B, Han H, Mao D, Chen J, Zeng Y and Xiong M: miR-155 affects osteosarcoma MG-63 cell autophagy induced by adriamycin through regulating PTEN-PI3K/AKT/mTOR signaling pathway. Cancer Biother Radiopharm. 33:32–38. 2018. View Article : Google Scholar : PubMed/NCBI