lncRNA TINCR promotes the development of cervical cancer via the miRNA‑7/mTOR axis <em>in vitro</em>

Liu,Xuan; Wang,Cui Xia; Feng,Qin; Zhang,Tao

doi:10.3892/etm.2023.12186

lncRNA TINCR promotes the development of cervical cancer via the miRNA‑7/mTOR axis in vitro

Authors:
- Xuan Liu
- Cui Xia Wang
- Qin Feng
- Tao Zhang
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Affiliations: Department of Gynecology, Women and Children's Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China, Department of Pediatrics, Eighth People's Hospital of Qingdao Shandong, Qingdao, Shandong 266000, P.R. China, Department of Imaging, Women and Children's Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China, Department of General Internal Medicine, Women and Children's Hospital, Qingdao University, Qingdao, Shandong 266000, P.R. China
Published online on: September 4, 2023 https://doi.org/10.3892/etm.2023.12186
Article Number: 487
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to examine the effects of the long non‑coding (lnc)RNA expressed by tissue differentiation‑inducing non‑protein coding RNA (TINCR) on cervical cancer development. For this purpose, adjacent normal and cancer tissues were obtained from patients with cervical cancer and the lncRNA TINCR level was examined using reverse transcription‑quantitative PCR (RT‑qPCR) and in situ hybridization. The association between lncRNA TINCR and the clinicopathological characteristics and prognosis of patients with cervical cancer was also analyzed. Furthermore, the expression levels of lncRNA TINCR, miRNA‑7, mTOR, hypoxia‑inducible factor 1 subunit α and VEGF were measured using RT‑qPCR and western blot analysis. Cell proliferation, apoptosis, and invasion and migration were examined using MTT assay, 5‑ethynyl‑2'‑deoxyuridine staining, flow cytometry, TUNEL assay, and Transwell and wound healing assays. The association between lncRNA TINCR, miRNA‑7 and mTOR was also examined using a luciferase assay. The results revealed that the lncRNA TINCR level was significantly increased in cervical cancer tissues and was associated with the overall survival of patients (low vs. high expression group; P=0.0391). LncRNA TINCR was also associated with the clinicopathological characteristics of patients with cervical cancer. Following the knockdown of lncRNA TINCR using small interfering (si)RNA, cell proliferation was significantly decreased and cell apoptosis was significantly increased (P<0.001 for both); cell invasion and migration were also significantly decreased (P<0.001 for both) following transfection with mimics miRNA‑7. Transfection with miRNA‑7 antisense oligonucleotide decreased the antitumor effects of si‑TINCR in Siha and HeLa cell lines. As shown using the dual‑luciferase assay, lncRNA TINCR could target miRNA‑7 and miRNA‑7 could directly regulate mTOR in HeLa and SiHa cell lines. In conclusion, the present study demonstrated that lncRNA TINCR could promote cervical cancer development via regulation of the miRNA‑7/mTOR axis in vitro.

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1	Small W Jr, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN and Gaffney DK: Cervical cancer: A global health crisis. Cancer. 123:2404–2412. 2017.PubMed/NCBI View Article : Google Scholar
2	Wardak S: Human Papillomavirus (HPV) and cervical cancer. Med Dosw Mikrobiol. 68:73–84. 2016.PubMed/NCBI
3	Shah CA, Beck T, Liao JB, Giannakopoulos NV, Veljovich D and Paley P: Surgical and oncologic outcomes after robotic radical hysterectomy as compared to open radical hysterectomy in the treatment of early cervical cancer. J Gynecol Oncol. 28(e82)2017.PubMed/NCBI View Article : Google Scholar
4	Schmitz SU, Grote P and Herrmann BG: Mechanisms of long non-coding RNA function in development and disease. Cell Mol Life Sci. 73:2491–2509. 2016.PubMed/NCBI View Article : Google Scholar
5	Dong L, Ding H, Li Y, Xue D and Liu Y: LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer. Cancer Manag Res. 10:2799–2807. 2018.PubMed/NCBI View Article : Google Scholar
6	Zhu ZJ and He JK: TINCR facilitates non-small cell lung cancer progression through BRAF-activated MAPK pathway. Biochem Biophys Res Commun. 497:971–977. 2018.PubMed/NCBI View Article : Google Scholar
7	Tian F, Xu J, Xue F, Guan E and Xu X: TINCR expression is associated with unfavorable prognosis in patients with hepatocellular carcinoma. Biosci Rep. 37(BSR20170301)2017.PubMed/NCBI View Article : Google Scholar
8	Xu J, Zeng W, Liu T, Wan Z, Yang X, Chen J and Liu F: lncRNA TINCR knockdown inhibits colon cancer cells via regulation of autophagy. Food Sci Nutr. 11:1965–1981. 2023.PubMed/NCBI View Article : Google Scholar
9	Luo H, Xu C, Le W, Ge B and Wang T: lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150. J Cell Biochem. 120:13487–13493. 2019.PubMed/NCBI View Article : Google Scholar
10	Luan X and Wang Y: LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p. J Gynecol Oncol. 29(e95)2018.PubMed/NCBI View Article : Google Scholar
11	Zhao W, Geng D, Li S, Chen Z and Sun M: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer. Cancer Med. 7:842–855. 2018.PubMed/NCBI View Article : Google Scholar
12	Peng CL, Zhao XJ, Wei CC and Wu JW: LncRNA HOTAIR promotes colon cancer development by down-regulating miRNA-34a. Eur Rev Med Pharmacol Sci. 23:5752–5761. 2019.PubMed/NCBI View Article : Google Scholar
13	Thiel J, Alter C, Luppus S, Eckstein A, Tan S, Führer D, Pastille E, Westendorf AM, Buer J and Hansen W: MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation. J Autoimmun. 96:94–103. 2019.PubMed/NCBI View Article : Google Scholar
14	Kara M, Yumrutas O, Ozcan O, Celik OI, Bozgeyik E, Bozgeyik I and Tasdemir S: Differential expressions of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma. Gene. 567:81–86. 2015.PubMed/NCBI View Article : Google Scholar
15	Yang Y, Li XJ, Li P and Guo XT: MicroRNA-145 regulates the proliferation, migration and invasion of human primary colon adenocarcinoma cells by targeting MAPK1. Int J Mol Med. 42:3171–3180. 2018.PubMed/NCBI View Article : Google Scholar
16	Zeng CY, Zhan YS, Huang J and Chen YX: MicroRNA-7 suppresses human colon cancer invasion and proliferation by targeting the expression of focal adhesion kinase. Mol Med Rep. 13:1297–1303. 2016.PubMed/NCBI View Article : Google Scholar
17	Xu N, Lian YJ, Dai X and Wang YJ: MiR-7 increases cisplatin sensitivity of gastric cancer cells through suppressing mTOR. Technol Cancer Res Treat. 16:1022–1030. 2017.PubMed/NCBI View Article : Google Scholar
18	Chen WS, Yen CJ, Chen YJ, Chen JY, Wang LY, Chiu SJ, Shih WL, Ho CY, Wei TT, Pan HL, et al: MiRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin. Oncotarget. 6:25962–25974. 2015.PubMed/NCBI View Article : Google Scholar
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
20	Tang Y, Cheung BB, Atmadibrata B, Marshall GM, Dinger ME, Liu PY and Liu T: The regulatory role of long non-coding RNAs in cancer. Cancer Lett. 391:12–19. 2017.PubMed/NCBI View Article : Google Scholar
21	McCabe EM and Rasmussen TP: lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions. Semin Cancer Biol. 75:38–48. 2021.PubMed/NCBI View Article : Google Scholar
22	Morgado-Palacin L, Brown JA, Martinez TF, Garcia-Pedrero JM, Forouhar F, Quinn SA, Reglero C, Vaughan J, Heydary YH, Donaldson C, et al: The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma. Nat Commun. 14(1328)2023.PubMed/NCBI View Article : Google Scholar
23	Zhang X, Yao J, Shi H, Gao B and Zhang L: LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis. Biol Chem. 400:663–675. 2019.PubMed/NCBI View Article : Google Scholar
24	Zhu X, Li H, Wu Y, Zhou J, Yang G and Wang W: LncRNA MEG3 promotes hepatic insulin resistance by serving as a competing endogenous RNA of miR-214 to regulate ATF4. Int J Mol Med. 43:345–357. 2019.PubMed/NCBI View Article : Google Scholar
25	Sehgal SN: Sirolimus: Its discovery, biological properties, and mechanism of action. Transplant Proc. 35 (3 Suppl):7S–14S. 2003.PubMed/NCBI View Article : Google Scholar
26	Wiederrecht GJ, Sabers CJ, Brunn GJ, Martin MM, Dumont FJ and Abraham RT: Mechanism of action of rapamycin: New insights into the regulation of G1-phase progression in eukaryotic cells. Prog Cell Cycle Res. 1:53–71. 1995.PubMed/NCBI View Article : Google Scholar
27	Edinger AL and Thompson CB: Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell. 13:2276–2288. 2002.PubMed/NCBI View Article : Google Scholar
28	Semenza GL: HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest. 123:3664–3671. 2013.PubMed/NCBI View Article : Google Scholar
29	Ryan HE, Lo J and Johnson RS: HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 17:3005–3015. 1998.PubMed/NCBI View Article : Google Scholar
30	Li L, Qu Y, Li J, Xiong Y, Mao M and Mu D: Relationship between HIF-1alpha expression and neuronal apoptosis in neonatal rats with hypoxia-ischemia brain injury. Brain Res. 1180:133–139. 2007.PubMed/NCBI View Article : Google Scholar
31	Chen Y, Peng GF, Han XZ, Wang W, Zhang GQ and Li X: Apoptosis prediction via inhibition of AKT signaling pathway by neogrifolin. Int J Clin Exp Pathol. 8:1154–1164. 2015.PubMed/NCBI
32	Kigure W, Fujii T, Sutoh T, Morita H, Katoh T, Yajima RN, Yamaguchi S, Tsutsumi S, Asao T and Kuwano H: The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor. Hepatogastroenterology. 60:277–280. 2013.PubMed/NCBI View Article : Google Scholar
33	Lugano R, Ramachandran M and Dimberg A: Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cell Mol Life Sci. 77:1745–1770. 2020.PubMed/NCBI View Article : Google Scholar
34	Li W, Petrimpol M, Molle KD, Hall MN, Battegay EJ and Humar R: Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2. Circ Res. 100:79–87. 2007.PubMed/NCBI View Article : Google Scholar
35	Tsai SY, Yang LY, Wu CH, Chang SF, Hsu CY, Wei CP, Leu SJ, Liaw J, Lee YH and Tsai MD: Injury-induced Janus kinase/protein kinase C-dependent phosphorylation of growth-associated protein 43 and signal transducer and activator of transcription 3 for neurite growth in dorsal root ganglion. J Neurosci Res. 85:321–331. 2007.PubMed/NCBI View Article : Google Scholar