LncRNA PCAT7 Promotes Non-small Cell Lung Cancer Progression by Activating MiR-486-5p/CDK4 Axis-mediated Cell Cycle

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Jun 15

PMID 35702078

Authors

Wenting Geng

Mengru Qiu

Dongbin Zhang

Peng Li

Gangyi Sun

Xi Zhou

Affiliations

Soon will be listed here.

Abstract

Objective: Lung cancer remains one of the common cancers worldwide. Both LncRNA PCAT7 and miR-486-5p are tightly correlated with NSCLC. However, the relationship between PCAT7 and miR-486-5p and the detailed mechanisms underlying the effect of PCAT7 on NSCLC are not discovered yet.

Methods: GEPIA and ENCORI databases were used to determine the expression of PCAT7 in different cancers. CCK8, colony formation and Transwell assay were used to confirm the ability of cells. Luciferase reporter gene assay was employed to estimate the luciferase activity of the gene. Flow cytometry was used to compare cell cycle of NSCLC cells after indicated treatment.

Results: GEPIA combined ENCORI database illustrated that LncRNA PCAT7 was upregulated dramatically in NSCLC. The mRNA level of PCAT7 cells was higher than that in normal cells. Silencing PCAT7 inhibited the progression of NSCLC cells significantly. Data from ENCORI website showed that miR-486-5p was the target of PCAT7 and was negatively controlled by it. The data also showed that CDK4 could be bound and negatively regulated by miR-486-5p. MiR-486-5p inhibitor or CDK4 could partly restore the inhibitory effect of PCAT7 in NSCLC cells. In addition, silencing PCAT7 could arrest cell cycle to S in addition to G2 stage while transfecting miR-486-5p inhibitor or CDK4 could partially eliminate the retarding effects.

Conclusion: In our study, we elaborated that LncRNA PCAT7 could promote the development of NSCLC cells by accelerating cell cycle miR-486-5p/CDK4 axis.

Citing Articles

Various LncRNA Mechanisms in Gene Regulation Involving miRNAs or RNA-Binding Proteins in Non-Small-Cell Lung Cancer: Main Signaling Pathways and Networks.

Braga E, Fridman M, Burdennyy A, Loginov V, Dmitriev A, Pronina I Int J Mol Sci. 2023; 24(17).

PMID: 37686426 PMC: 10487663. DOI: 10.3390/ijms241713617.

References

Wang B, Jiang H, Wang L, Chen X, Wu K, Zhang S . Increased MIR31HG lncRNA expression increases gefitinib resistance in non-small cell lung cancer cell lines through the EGFR/PI3K/AKT signaling pathway. Oncol Lett. 2017; 13(5):3494-3500. PMC: 5431660. DOI: 10.3892/ol.2017.5878. View

Horie M, Kaczkowski B, Ohshima M, Matsuzaki H, Noguchi S, Mikami Y . Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC. Mol Cancer Res. 2017; 15(10):1354-1365. DOI: 10.1158/1541-7786.MCR-17-0191. View

Yu X, Lin Q, Liu F, Yang F, Mao J, Chen X . LncRNA TMPO-AS1 facilitates the proliferation and metastasis of NSCLC cells by up-regulating ERBB2 via sponging miR-204-3p. Int J Immunopathol Pharmacol. 2020; 34:2058738420958947. PMC: 7520928. DOI: 10.1177/2058738420958947. View

Shi L, Liu S, Zhao W, Shi J . miR-483-5p and miR-486-5p are down-regulated in cumulus cells of metaphase II oocytes from women with polycystic ovary syndrome. Reprod Biomed Online. 2015; 31(4):565-72. DOI: 10.1016/j.rbmo.2015.06.023. View

Li J, Li Z, Zheng W, Li X, Wang Z, Cui Y . PANDAR: a pivotal cancer-related long non-coding RNA in human cancers. Mol Biosyst. 2017; 13(11):2195-2201. DOI: 10.1039/c7mb00414a. View

Xing Z, Zhang Z, Gao Y, Zhang X, Kong X, Zhang J . The lncRNA LINC01194/miR-486-5p Axis Facilitates Malignancy in Non-Small Cell Lung Cancer via Regulating CDK4. Onco Targets Ther. 2020; 13:3151-3163. PMC: 7167278. DOI: 10.2147/OTT.S235037. View

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob S, Patel T . MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007; 133(2):647-58. PMC: 4285346. DOI: 10.1053/j.gastro.2007.05.022. View

Ramos A, Attenello F, Lim D . Uncovering the roles of long noncoding RNAs in neural development and glioma progression. Neurosci Lett. 2016; 625:70-9. PMC: 5094911. DOI: 10.1016/j.neulet.2015.12.025. View

Yu L, Todd N, Xing L, Xie Y, Zhang H, Liu Z . Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2011; 127(12):2870-8. PMC: 3545471. DOI: 10.1002/ijc.25289. View

10.

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

11.

Ou L, Wang D, Zhang H, Yu Q, Hua F . Decreased Expression of miR-138-5p by lncRNA H19 in Cervical Cancer Promotes Tumor Proliferation. Oncol Res. 2017; 26(3):401-410. PMC: 7844697. DOI: 10.3727/096504017X15017209042610. View

12.

Peng Y, Dai Y, Hitchcock C, Yang X, Kassis E, Liu L . Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer. Proc Natl Acad Sci U S A. 2013; 110(37):15043-8. PMC: 3773758. DOI: 10.1073/pnas.1307107110. View

13.

Zhang Y, Li X, Hou Y, Fang N, You J, Zhou Q . The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer. Acta Pharmacol Sin. 2017; 38(3):371-381. PMC: 5342664. DOI: 10.1038/aps.2016.133. View

14.

He P, Zhang Z, Huang G, Wang H, Xu D, Liao W . miR-141 modulates osteoblastic cell proliferation by regulating the target gene of lncRNA H19 and lncRNA H19-derived miR-675. Am J Transl Res. 2016; 8(4):1780-8. PMC: 4859907. View

15.

Xiao C, Rajewsky K . MicroRNA control in the immune system: basic principles. Cell. 2009; 136(1):26-36. DOI: 10.1016/j.cell.2008.12.027. View

16.

Oh H, Tan A, Das K, Ooi C, Deng N, Tan I . Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer. Clin Cancer Res. 2011; 17(9):2657-67. DOI: 10.1158/1078-0432.CCR-10-3152. View

17.

Gao Z, Yuan W, Yuan J, Yuan K, Wang Y . miR-486-5p functions as an oncogene by targeting PTEN in non-small cell lung cancer. Pathol Res Pract. 2018; 214(5):700-705. DOI: 10.1016/j.prp.2018.03.013. View

18.

Shen J, Liu Z, Todd N, Zhang H, Liao J, Yu L . Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer. 2011; 11:374. PMC: 3175224. DOI: 10.1186/1471-2407-11-374. View

19.

Li Z, Shen J, Chan M, Wu W . TUG1: a pivotal oncogenic long non-coding RNA of human cancers. Cell Prolif. 2016; 49(4):471-5. PMC: 6496395. DOI: 10.1111/cpr.12269. View

20.

Wang F, Ying H, He B, Pan Y, Deng Q, Sun H . Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget. 2015; 6(10):7899-917. PMC: 4480724. DOI: 10.18632/oncotarget.3219. View