Downregulation of long non‑coding RNA GACAT1 suppresses proliferation and induces apoptosis of NSCLC cells by sponging microRNA‑422a Retraction in /10.3892/ijmm.2023.5325

Zhong,Youqing; Lin,Hui; Li,Qi; Liu,Chang; Zhong,Lei

doi:10.3892/ijmm.2020.4826

Downregulation of long non‑coding RNA GACAT1 suppresses proliferation and induces apoptosis of NSCLC cells by sponging microRNA‑422a

Retraction in: /10.3892/ijmm.2023.5325

Authors:
- Youqing Zhong
- Hui Lin
- Qi Li
- Chang Liu
- Lei Zhong
View Affiliations

Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 571100, P.R. China, Department of Anesthesia, Hainan General Hospital, Haikou, Hainan 570311, P.R. China, Clinical Laboratory, Ganzhou People's Hospital of Jiangxi Province, Ganzhou, Jiangxi 341000, P.R. China
Published online on: December 22, 2020 https://doi.org/10.3892/ijmm.2020.4826
Pages: 659-667
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Increasing evidence has demonstrated the important roles of long non‑coding (lnc) RNA in non‑small cell lung cancer (NSCLC). lncRNA gastric cancer‑associated transcript 1 (GACAT1) has been reported to play an oncogenic role in different types of cancer; however, the function of GACAT1 in NSCLC remains unclear. The present study found that GACAT1 was overexpressed in NSCLC tissues and was associated with poor outcomes in patients with NSCLC. Functional experiments revealed that GACAT1 downregulation inhibited proliferation, induced apoptosis and cell cycle arrest of 2 NSCLC cell lines. GACAT1 was found to target microRNA(miR)‑422a mechanically and negatively regulated miR‑422a expression. Reduced expression of miR‑422a in NSCLC tissues was inversely correlated with that of GACAT1. Furthermore, YY1 transcription factor (YY1) was identified as a downstream miR‑422a target. Reduced expression of GACAT1 inactivated YY1 by sponging miR‑422a in NSCLC cells. YY1 reintroduction reversed the reduced proliferation of NSCLC cells via GACAT1 knockdown. Taken together, these results revealed the novel role of the GACAT1/miR‑422a pathway in the progression of NSCLC cell lines, providing a possible therapeutic strategy for NSCLC treatment.

View Figures

View References

1	Saintigny P and Burger JA: Recent advances in non-small cell lung cancer biology and clinical management. Discov Med. 13:287–297. 2012.PubMed/NCBI
2	Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI
3	Uzel EK, Figen M and Uzel Ö: Radiotherapy in lung cancer: Current and future role. Sisli Etfal Hastan Tip Bull. 53:353–360. 2019.
4	Mulherkar R, Grewal AS and Berman AT: Emerging role of immunotherapy in locally advanced non-small cell lung cancer. Clin Adv Hematol Oncol. 18:212–217. 2020.PubMed/NCBI
5	Friedlaender A, Kim C and Addeo A: Rethinking the optimal duration of immune checkpoint inhibitors in non-small cell lung cancer throughout the COVID-19 pandemic. Front Oncol. 10:8622020. View Article : Google Scholar : PubMed/NCBI
6	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar : PubMed/NCBI
7	Batista PJ and Chang HY: Long noncoding RNAs: Cellular address codes in development and disease. Cell. 152:1298–1307. 2013. View Article : Google Scholar : PubMed/NCBI
8	Mercer TR, Dinger ME and Mattick J: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
9	Do H and Kim W: Roles of oncogenic long non-coding RNAs in cancer development. Genomics Inform. 16:e182018. View Article : Google Scholar
10	Wang L, Ma L, Xu F, Zhai W, Dong S, Yin L, Liu J and Yu Z: Role of long non-coding RNA in drug resistance in non-small cell lung cancer. Thorac Cancer. 9:761–768. 2018. View Article : Google Scholar : PubMed/NCBI
11	Huang Q: Predictive relevance of ncRNAs in non-small-cell lung cancer patients with radiotherapy: A review of the published data. Biomark Med. 12:1149–1159. 2018. View Article : Google Scholar : PubMed/NCBI
12	Lu T, Wang Y, Chen D, Liu J and Jiao W: Potential clinical application of lncRNAs in non-small cell lung cancer. Onco Targets Ther. 11:8045–8052. 2018. View Article : Google Scholar : PubMed/NCBI
13	Ghafouri-Fard S, Shoorei H, Branicki W and Taheri M: Non-coding RNA profile in lung cancer. Exp Mol Pathol. 114:1044112020. View Article : Google Scholar : PubMed/NCBI
14	Dai SP, Jin J and Li WM: Diagnostic efficacy of long non-coding RNA in lung cancer: A systematic review and meta-analysis. Postgrad Med J. 94:578–587. 2018. View Article : Google Scholar : PubMed/NCBI
15	Peng W, Wang J, Shan B, Peng Z, Dong Y, Shi W, He D, Cheng Y, Zhao W, Zhang C, et al: Diagnostic and prognostic potential of circulating long non-coding RNAs in non small cell lung cancer. Cell Physiol Biochem. 49l:816–827. 2018. View Article : Google Scholar
16	He R, Zhang FH and Shen N: lncRNA FEZF1-AS1 enhances epithelial-mesenchymal transition (EMT) through suppressing E-cadherin and regulating WNT pathway in non-small cell lung cancer (NSCLC). Biomed Pharmacother. 95:331–338. 2017. View Article : Google Scholar : PubMed/NCBI
17	Sun W, Zu Y, Fu X and Deng Y: Knockdown of lncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy. Oncol Rep. 38:3347–3354. 2017.PubMed/NCBI
18	Ying J, Yang J and Liu Y: lncARSR promotes non-small-cell lung cancer progression via regulating PTEN/akt. Am J Transl Res. 12:857–866. 2020.PubMed/NCBI
19	Xiao B and Guo J: Long noncoding RNA AC096655.1-002 has been officially named as gastric cancer-associated transcript 1, GACAT1. Tumour Biol. 34:32712013. View Article : Google Scholar : PubMed/NCBI
20	Li PF, Chen SC, Xia T, Jiang XM, Shao YF, Xiao BX and Guo JM: Non-coding RNAs and gastric cancer. World J Gastroenterol. 20:5411–5419. 2014. View Article : Google Scholar : PubMed/NCBI
21	Xia T, Liao Q, Jiang X, Shao Y, Xiao B, Xi Y and Guo J: Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep. 4:60882014. View Article : Google Scholar : PubMed/NCBI
22	Shi X, Wang X and Hua Y: LncRNA GACAT1 promotes gastric cancer cell growth, invasion and migration by regulating miR-149-mediated Of ZBTB2 and SP1. J Cancer. 9:3715–3722. 2018. View Article : Google Scholar : PubMed/NCBI
23	Wang Q, Xue J, Ren Q, Li X and Qiu X: Long-chain non-coding RNA GACAT1 promotes development and progression of breast cancer by targeting microRNA-875-3p. Oncol Lett. 19:2547–2553. 2020.PubMed/NCBI
24	Zhao Y, Wang H, Wu C, Yan M, Wu H, Wang J, Yang X and Shao Q: Construction and investigation of lncRNA-associated ceRNA regulatory network in papillary thyroid cancer. Oncol Rep. 39:1197–1206. 2018.PubMed/NCBI
25	Li F, Huang C, Li Q and Wu X: Construction and comprehensive analysis for dysregulated long non-coding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in gastric cancer. Med Sci Monit. 24:37–49. 2018. View Article : Google Scholar : PubMed/NCBI
26	Zhang Z, Qian W, Wang S, Ji D, Wang Q, Li J, Peng W, Gu J, Hu T, Ji B, et al: Analysis of lncRNA-associated ceRNA network reveals potential lncRNA biomarkers in human colon adenocarcinoma. Cell Physiol Biochem. 49:1778–1791. 2018. View Article : Google Scholar : PubMed/NCBI
27	Mohr AM and Mott JL: Overview of microRNA biology. Semin Liver Dis. 35:3–11. 2015. View Article : Google Scholar : PubMed/NCBI
28	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
29	Lu TX and Rothenberg ME: MicroRNA. J Allergy Clin Immunol. 141:1202–1207. 2018. View Article : Google Scholar :
30	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Ann Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
31	Thomson DW and Dinger ME: Endogenous microRNA sponges: Evidence and controversy. Nat Rev Genet. 17:272–283. 2016. View Article : Google Scholar : PubMed/NCBI
32	Qi X, Zhang DH, Wu N, Xiao JH, Wang X and Ma W: CeRNA in cancer: Possible functions and clinical implications. J Med Genet. 52:710–718. 2015. View Article : Google Scholar : PubMed/NCBI
33	Zhou Z, Lin Z, He Y, Pang X, Wang Y, Ponnusamy M, Ao X, Shan P, Tariq MA, Li P and Wang J: The long noncoding RNA D63785 regulates chemotherapy sensitivity in human gastric cancer by targeting miR-422a. Mol Ther Nucleic Acids. 12:405–419. 2018. View Article : Google Scholar : PubMed/NCBI
34	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
35	Schmitt AM and Chang HY: Long noncoding RNAs in cancer pathways. Cancer Cell. 29:452–463. 2016. View Article : Google Scholar : PubMed/NCBI
36	Huarte M: The emerging role of lncRNAs in cancer. Nat Med. 21:1253–1261. 2015. View Article : Google Scholar : PubMed/NCBI
37	Liu M, Xiusheng H, Xiao X and Wang Y: Overexpression of miR-422a inhibits cell proliferation and invasion, and enhances chemosensitivity in osteosarcoma cells. Oncol Rep. 36:3371–3378. 2016. View Article : Google Scholar : PubMed/NCBI
38	Zheng GX, Qu AL, Yang YM, Zhang X, Zhang SC and Wang CX: miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer. World J Gastroenterol. 22:5589–5597. 2016. View Article : Google Scholar : PubMed/NCBI
39	Liang H, Wang R, Jin Y, Li J and Zhang S: MiR-422a acts as a tumor suppressor in glioblastoma by targeting PIK3CA. Am J Cancer Res. 6:1695–1707. 2016.PubMed/NCBI
40	Wei WT, Nian XX, Wang SY, Jiao HL, Wang YX, Xiao ZY, Yang RW, Ding YQ, Ye YP and Liao WT: miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1. Cancer Cell Int. 17:912017. View Article : Google Scholar : PubMed/NCBI
41	Zou Y, Chen Y, Yao S, Deng G, Liu D, Yuan X, Liu S, Rao J, Xiong H, Yuan X, et al: MiR-422a weakened breast cancer stem cells properties by targeting PLP2. Cancer Biol Ther. 19:436–444. 2018. View Article : Google Scholar : PubMed/NCBI
42	He Z, Li Z, Zhang X, Yin K, Wang W, Xu Z, Li B, Zhang L, Xu J, Sun G, et al: MiR-422a regulates cellular metabolism and malignancy by targeting pyruvate dehydrogenase kinase 2 in gastric cancer. Cell Death Dis. 9:5052018. View Article : Google Scholar : PubMed/NCBI
43	Khachigian LM: The yin and yang of YY1 in tumor growth and suppression. Int J Cancer. 143:460–465. 2018. View Article : Google Scholar : PubMed/NCBI
44	Sarvagalla S, Kolapalli SP and Vallabhapurapu S: The two sides of YY1 in cancer: A friend and a foe. Front Oncol. 9:12302019. View Article : Google Scholar : PubMed/NCBI
45	Meliala IT, Hosea R, Kasim V and Wu S: The biological implications of yin yang 1 in the hallmarks of cancer. Theranostics. 10:4183–4200. 2020. View Article : Google Scholar : PubMed/NCBI
46	Liu D, Zhang J, Wu Y, Shi G, Yuan H, Lu Z, Zhu Q, Wu P, Lu C, Guo F, et al: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway. Int J Cancer. 142:1392–1404. 2018. View Article : Google Scholar
47	Grönroos E, Terentiev AA, Punga T and Ericsson J: YY1 inhibits the activation of the p53 tumor suppressor in response to geno-toxic stress. Proc Natil Acad Sci USA. 101:12165–12170. 2004. View Article : Google Scholar
48	Sui G, Affar El B and Shi Y, Brignone C, Wall NR, Yin P, Donohoe M, Luke MP, Calvo D, Grossman SR and Shi Y: Yin yang 1 is a negative regulator of p53. Cell. 117:859–872. 2004. View Article : Google Scholar : PubMed/NCBI