lncRNA TPT1‑AS1 knockdown inhibits liver cancer cell proliferation, migration and invasion

Li,Hao; Jin,Jing; Xian,Jianchun; Wang,Wei

doi:10.3892/mmr.2021.12422

lncRNA TPT1‑AS1 knockdown inhibits liver cancer cell proliferation, migration and invasion

Authors:
- Hao Li
- Jing Jin
- Jianchun Xian
- Wei Wang
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Affiliations: Department of Infectious Diseases, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China, Department of Rehabilitation Medicine, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
Published online on: September 7, 2021 https://doi.org/10.3892/mmr.2021.12422
Article Number: 782
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) tumor protein translationally controlled 1 antisense RNA 1 (TPT1‑AS1) serves as an oncogene in several tumors, including ovarian and cervical cancer. However, the functional role of TPT1‑AS1 in liver cancer (LC) is not completely understood. The present study aimed to explore the role of TPT1‑AS1 in LC. In this study, the reverse transcription‑quantitative PCR results demonstrated that TPT1‑AS1 expression was significantly upregulated in LC tissues and cell lines compared with adjacent paracancerous tissues and THLE‑3 cells, respectively. Elevated TPT1‑AS1 expression was significantly associated with TNM stage lymph node metastasis and poor prognosis in patients with LC, as determined via χ² and Kaplan‑Meier survival analyses. By constructing TPT1‑AS1 knockdown LC cell lines (HepG2 and SNU‑182), loss‑of‑function experiments, including Cell Counting Kit‑8, colony formation, flow cytometry, wound healing and Transwell assays, were performed to explore the function role of TPT1‑AS1 in LC in vitro. The results demonstrated that TPT1‑AS1 knockdown inhibited LC cell proliferation, G₁/S transition, migration and invasion compared with the small interfering RNA (si)‑negative control (NC) group. Mechanistically, TPT1‑AS1 knockdown markedly decreased CDK4, N‑cadherin and Vimentin expression levels, but notably increased p21 and E‑cadherin expression levels compared with the si‑NC group. Therefore, the results of the present study suggested that TPT1‑AS1 might serve as a promising therapeutic target for LC treatment.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Qin G, Dang M, Gao H, Wang H, Luo F and Chen R: Deciphering the protein-protein interaction network regulating hepatocellular carcinoma metastasis. Biochim Biophys Acta Proteins Proteom. 1865:1114–1122. 2017. View Article : Google Scholar : PubMed/NCBI
3	El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI
4	Carr BI: Hepatocellular carcinoma: Current management and future trends. Gastroenterology. 127 (Suppl 1):S218–S224. 2004. View Article : Google Scholar : PubMed/NCBI
5	Llovet JM: Updated treatment approach to hepatocellular carcinoma. J Gastroenterol. 40:225–235. 2005. View Article : Google Scholar : PubMed/NCBI
6	Lopez PM, Villanueva A and Llovet JM: Systematic review: Evidence-based management of hepatocellular carcinoma-an updated analysis of randomized controlled trials. Aliment Pharmacol Ther. 23:1535–1547. 2006. View Article : Google Scholar : PubMed/NCBI
7	Chu C, Spitale RC and Chang HY: Technologies to probe functions and mechanisms of long noncoding RNAs. Nat Struct Mol Biol. 22:29–35. 2015. View Article : Google Scholar : PubMed/NCBI
8	Kopp F and Mendell JT: Functional classification and experimental dissection of long noncoding RNAs. Cell. 172:393–407. 2018. View Article : Google Scholar : PubMed/NCBI
9	Chen J, Wang R, Zhang K and Chen LB: Long non-coding RNAs in non-small cell lung cancer as biomarkers and therapeutic targets. J Cell Mol Med. 18:2425–2436. 2014. View Article : Google Scholar : PubMed/NCBI
10	Yang Y, Chen L, Gu J, Zhang H, Yuan J, Lian Q, Lv G, Wang S, Wu Y, Yang YT, et al: Recurrently deregulated lncRNAs in hepatocellular carcinoma. Nat Commun. 8:144212017. View Article : Google Scholar : PubMed/NCBI
11	Wu S, Liu J, Wang X, Li M, Chen Z and Tang Y: Aberrant expression of the long non-coding RNA GHRLOS and its prognostic significance in patients with colorectal cancer. J Cancer. 8:4040–4047. 2017. View Article : Google Scholar : PubMed/NCBI
12	Jiang H, Shi X, Ye G, Xu Y, Xu J, Lu J and Lu W: Up-regulated long non-coding RNA DUXAP8 promotes cell growth through repressing Krüppel-like factor 2 expression in human hepatocellular carcinoma. Onco Targets Ther. 12:7429–7436. 2019. View Article : Google Scholar : PubMed/NCBI
13	Zheng Y, Nie P and Xu S: Long noncoding RNA linc00467 plays an oncogenic role in hepatocellular carcinoma by regulating the miR-18a-5p/NEDD9 axis. J Cell Biochem. 121:3135–3144. 2020. View Article : Google Scholar : PubMed/NCBI
14	Deng Y, Wei Z, Huang M, Xu G, Wei W, Peng B, Nong S and Qin H: Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p. J Cell Mol Med. 24:1848–1865. 2020. View Article : Google Scholar : PubMed/NCBI
15	Wang W, Yang F, Zhang L, Chen J, Zhao Z, Wang H, Wu F, Liang T, Yan X, Li J, et al: LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas. Oncotarget. 7:77225–77236. 2016. View Article : Google Scholar : PubMed/NCBI
16	Zan XY and Li L: Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas. Oncol Lett. 17:4369–4374. 2019.PubMed/NCBI
17	Jiang H, Huang G, Zhao N, Zhang T, Jiang M, He Y, Zhou X and Jiang X: Long non-coding RNA TPT1-AS1 promotes cell growth and metastasis in cervical cancer via acting AS a sponge for miR-324-5p. J Exp Clin Cancer Res. 37:1692018. View Article : Google Scholar : PubMed/NCBI
18	Jia L, Song Y, Mu L, Li Q, Tang J, Yang Z and Meng W: Long noncoding RNA TPT1-AS1 downregulates the microRNA-770-5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation. J Cell Physiol. 235:3679–3689. 2020. View Article : Google Scholar : PubMed/NCBI
19	Tang J, Huang F, Wang H, Cheng F, Pi Y, Zhao J and Li Z: Knockdown of TPT1-AS1 inhibits cell proliferation, cell cycle G1/S transition, and epithelial-mesenchymal transition in gastric cancer. Bosn J Basic Med Sci. 21:39–46. 2021.PubMed/NCBI
20	Mirsadraee S, Oswal D, Alizadeh Y, Caulo A and van Beek E Jr: The 7th lung cancer TNM classification and staging system: Review of the changes and implications. World J Radiol. 4:128–134. 2012. View Article : Google Scholar : PubMed/NCBI
21	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. View Article : Google Scholar : PubMed/NCBI
22	Huang ZL, Li W, Chen QF, Wu PH and Shen LJ: Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets. World J Gastrointest Oncol. 11:983–997. 2019. View Article : Google Scholar : PubMed/NCBI
23	Wu W, Gao H, Li X, Zhu Y, Peng S, Yu J, Zhan G, Wang J, Liu N and Guo X: LncRNA TPT1-AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression. Cancer Sci. 110:1587–1598. 2019. View Article : Google Scholar : PubMed/NCBI
24	He Y, Vogelstein B, Velculescu VE, Papadopoulos N and Kinzler KW: The antisense transcriptomes of human cells. Science. 322:1855–1857. 2008. View Article : Google Scholar : PubMed/NCBI
25	Munroe SH and Zhu J: Overlapping transcripts, double-stranded RNA and antisense regulation: A genomic perspective. Cell Mol Life Sci. 63:2102–1218. 2006. View Article : Google Scholar : PubMed/NCBI
26	Faghihi MA and Wahlestedt C: Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol. 10:637–643. 2009. View Article : Google Scholar : PubMed/NCBI
27	Wang Y, Yang L, Chen T, Liu X, Guo Y, Zhu Q, Tong X, Yang W, Xu Q, Huang D and Tu K: A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol Cancer. 18:282019. View Article : Google Scholar : PubMed/NCBI
28	Yin L, Chen Y, Zhou Y, Deng G, Han Y, Guo C, Li Y, Zeng S and Shen H: Increased long noncoding RNA LASP1-AS is critical for hepatocellular carcinoma tumorigenesis via upregulating LASP1. J Cell Physiol. 234:13493–13509. 2019. View Article : Google Scholar : PubMed/NCBI
29	Ji D, Hu G, Zhang X, Yu T and Yang J: Long non-coding RNA DSCAM-AS1 accelerates the progression of hepatocellular carcinoma via sponging miR-338-3p. Am J Transl Res. 11:4290–4302. 2019.PubMed/NCBI
30	Ye D, Luo H, Lai Z, Zou L, Zhu L, Mao J, Jacob T, Ye W, Wang L and Chen L: ClC-3 chloride channel proteins regulate the cell cycle by up-regulating cyclin D1-CDK4/6 through suppressing p21/p27 expression in nasopharyngeal carcinoma cells. Sci Rep. 6:302762016. View Article : Google Scholar : PubMed/NCBI
31	Liu J, Min L, Zhu S, Guo Q, Li H, Zhang Z, Zhao Y, Xu C and Zhang S: Cyclin-dependent kinase inhibitor 3 promoted cell proliferation by driving cell cycle from G1 to S phase in esophageal squamous cell carcinoma. J Cancer. 10:1915–1922. 2019. View Article : Google Scholar : PubMed/NCBI
32	Wang F, Qi X, Li Z, Jin S, Xie Y and Zhong H: lncRNA CADM1-AS1 inhibits cell-cycle progression and invasion via PTEN/AKT/GSK-3β axis in hepatocellular carcinoma. Cancer Manag Res. 11:3813–3828. 2019. View Article : Google Scholar : PubMed/NCBI
33	Ma C, Huang S, Xu L, Tian L, Yang Y and Wang J: Transcription co-activator P300 activates Elk1-aPKC-ι signaling mediated epithelial-to-mesenchymal transition and malignancy in hepatocellular carcinoma. Oncogenesis. 9:322020. View Article : Google Scholar : PubMed/NCBI
34	Zhang Y, Xu J, Zhang S, An J, Zhang J, Huang J and Jin Y: HOXA-AS2 promotes proliferation and induces epithelial-mesenchymal transition via the miR-520c-3p/GPC3 axis in hepatocellular carcinoma. Cell Physiol Biochem. 50:2124–2138. 2018. View Article : Google Scholar : PubMed/NCBI
35	Li Y, Liu G, Li X, Dong H, Xiao W and Lu S: Long non-coding RNA SBF2-AS1 promotes hepatocellular carcinoma progression through regulation of miR-140-5p-TGFBR1 pathway. Biochem Biophys Res Commun. 503:2826–2832. 2018. View Article : Google Scholar : PubMed/NCBI