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LINC00839/miR-519d-3p/JMJD6 axis modulated cell viability, apoptosis, migration and invasiveness of lung cancer cells
Affiliations- The Second Affiliated Hospital of Jiaxing University, Pulmonary and Critical Care Medicine, Jiaxing, China
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Abstract
Introduction. Long noncoding RNAs are associated with progressions of lung cancer. LINC00839 has been
dysregulated in osteosarcoma, breast cancer and lung cancer (LC). As an upregulated lncRNA, the roles of
LINC00839 in lung cancer remain unclear.
Material and methods. RNA expressions of LINC00839, miR-519d-3p and JMJD6 were assessed using RT-qPCR and JMJD6 protein expression were analyzed through Western blot. Meanwhile, viabilities of A549 and H460 LC cells transfected by siNC, siLINC00839, oeNC, oeLINC00839, NC mimics, miR-519d-3p mimics and oeLINC00839 with siJMJD6 were examined with CCK-8 assay while apoptosis was examined using flow cytometry. Meanwhile, migration and invasiveness were analyzed using transwell assays. Bindings between LINC00839 and miR-519d-3p, miR-519d-3p and JMJD6 were measured by luciferase reporter assays.
Results. LINC00839 was upregulated in LC cells and its knockdown resulted in reduced cell viability, migratory ability and invasion with increased cell apoptosis. MiR-519d-3p was the target gene of LINC00839 and its expression was reduced by LINC00839 overexpression. JMJD6 was directly targeted and suppressed at the level of mRNA and protein expression by miR-519d-3p. Moreover, miR-519d-3p overexpression resulted in low LC cell viability, migration, invasiveness but a high apoptosis rate. Furthermore, mRNA and protein expressions of JMJD6 were upregulated by LINC00839 overexpression. LINC00839 competitively sponged miR-519d-3p, increasing JMJD6 expression, LC cell viability, invasion, migratory abilities and decreasing apoptosis rates in A549 and H460 lung cancer cells, which were hindered after JMJD6 knockdown.
Conclusions. LINC00839/miR-519d-3p/JMJD6 axis mediated cell viability, apoptosis, and migration and invasiveness of H460 lung cancer cells.
Abstract
Introduction. Long noncoding RNAs are associated with progressions of lung cancer. LINC00839 has been
dysregulated in osteosarcoma, breast cancer and lung cancer (LC). As an upregulated lncRNA, the roles of
LINC00839 in lung cancer remain unclear.
Material and methods. RNA expressions of LINC00839, miR-519d-3p and JMJD6 were assessed using RT-qPCR and JMJD6 protein expression were analyzed through Western blot. Meanwhile, viabilities of A549 and H460 LC cells transfected by siNC, siLINC00839, oeNC, oeLINC00839, NC mimics, miR-519d-3p mimics and oeLINC00839 with siJMJD6 were examined with CCK-8 assay while apoptosis was examined using flow cytometry. Meanwhile, migration and invasiveness were analyzed using transwell assays. Bindings between LINC00839 and miR-519d-3p, miR-519d-3p and JMJD6 were measured by luciferase reporter assays.
Results. LINC00839 was upregulated in LC cells and its knockdown resulted in reduced cell viability, migratory ability and invasion with increased cell apoptosis. MiR-519d-3p was the target gene of LINC00839 and its expression was reduced by LINC00839 overexpression. JMJD6 was directly targeted and suppressed at the level of mRNA and protein expression by miR-519d-3p. Moreover, miR-519d-3p overexpression resulted in low LC cell viability, migration, invasiveness but a high apoptosis rate. Furthermore, mRNA and protein expressions of JMJD6 were upregulated by LINC00839 overexpression. LINC00839 competitively sponged miR-519d-3p, increasing JMJD6 expression, LC cell viability, invasion, migratory abilities and decreasing apoptosis rates in A549 and H460 lung cancer cells, which were hindered after JMJD6 knockdown.
Conclusions. LINC00839/miR-519d-3p/JMJD6 axis mediated cell viability, apoptosis, and migration and invasiveness of H460 lung cancer cells.
Keywords
LINC00839; miR-519d-3p; JMJD6; lung cancer
About this articleTitle
LINC00839/miR-519d-3p/JMJD6 axis modulated cell viability, apoptosis, migration and invasiveness of lung cancer cells
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Original paper
Pages
271-281
Published online
2021-11-04
Page views
7669
Article views/downloads
540
DOI
Pubmed
Bibliographic record
Folia Histochem Cytobiol 2021;59(4):271-281.
Keywords
LINC00839
miR-519d-3p
JMJD6
lung cancer
Authors
Xiaoyan Yu
Yifei Jiang
Xun Hu
Xiang Ge
References (37)- Mao Y, Yang D, He J, et al. Epidemiology of Lung Cancer. Surg Oncol Clin N Am. 2016; 25(3): 439–445.
- Ghafouri-Fard S, Shoorei H, Branicki W, et al. Non-coding RNA profile in lung cancer. Exp Mol Pathol. 2020; 114: 104411.
- Bade BC, Dela Cruz CS. Lung Cancer 2020: Epidemiology, Etiology, and Prevention. Clin Chest Med. 2020; 41(1): 1–24.
- Martin P, Leighl NB. Review of the use of pretest probability for molecular testing in non-small cell lung cancer and overview of new mutations that may affect clinical practice. Ther Adv Med Oncol. 2017; 9(6): 405–414.
- Nagano T, Fraser P. No-nonsense functions for long noncoding RNAs. Cell. 2011; 145(2): 178–181.
- Luo H, Xu C, Le W, et al. lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150. J Cell Biochem. 2019; 120(8): 13487–13493.
- Luo J, Wang K, Yeh S, et al. LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling. Nat Commun. 2019; 10(1): 2571.
- Robinson EK, Covarrubias S, Carpenter S. The how and why of lncRNA function: An innate immune perspective. Biochim Biophys Acta Gene Regul Mech. 2020; 1863(4): 194419.
- Zhang Y, Guo H, Ma Li, et al. Long Noncoding RNA LINC00839 Promotes the Malignant Progression of Osteosarcoma by Competitively Binding to MicroRNA-454-3p and Consequently Increasing c-Met Expression. Cancer Manag Res. 2020; 12: 8975–8987.
- Yang L, Pei L, Yi J. LINC00839 Regulates Proliferation, Migration, Invasion, Apoptosis and Glycolysis in Neuroblastoma Cells Through miR-338-3p/GLUT1 Axis. Neuropsychiatr Dis Treat. 2021; 17: 2027–2040.
- Tian Y, Yu M, Sun Li, et al. Distinct Patterns of mRNA and lncRNA Expression Differences Between Lung Squamous Cell Carcinoma and Adenocarcinoma. J Comput Biol. 2020; 27(7): 1067–1078.
- Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010; 79: 351–379.
- Li YY, Shao JP, Zhang SP, et al. miR-519d-3p Inhibits Cell Proliferation and Invasion of Gastric Cancer by Downregulating B-Cell Lymphoma 6. Cytogenet Genome Res. 2018; 154(1): 12–19.
- Zhan S, Wang C, Yin F. MicroRNA-29c inhibits proliferation and promotes apoptosis in non-small cell lung cancer cells by targeting VEGFA. Mol Med Rep. 2018; 17(5): 6705–6710.
- Kwok J, O'Shea M, Hume DA, et al. Jmjd6, a JmjC Dioxygenase with Many Interaction Partners and Pleiotropic Functions. Front Genet. 2017; 8: 32.
- Wang K, Du B, Xu B, et al. JMJD6-STAT3 axis promotes autophagy in osteosarcoma cancer cells by regulating ATG. Biofactors. 2020; 46(5): 839–848.
- Zhang Z, Yang Y, Zhang X. MiR-770 inhibits tumorigenesis and EMT by targeting JMJD6 and regulating WNT/β-catenin pathway in non-small cell lung cancer. Life Sci. 2017; 188: 163–171.
- Wan J, Liu H, Yang L, et al. JMJD6 promotes hepatocellular carcinoma carcinogenesis by targeting CDK4. Int J Cancer. 2019; 144(10): 2489–2500.
- Wong M, Sun Y, Xi Z, et al. JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma. Nat Commun. 2019; 10(1): 3319.
- Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483): 344–352.
- Long J, Bai Yi, Yang X, et al. Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for hepatocellular carcinoma. Cancer Cell Int. 2019; 19: 90.
- Zhou RS, Zhang EX, Sun QF, et al. Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue. BMC Cancer. 2019; 19(1): 779.
- Wang J, Su Z, Lu S, et al. LncRNA HOXA-AS2 and its molecular mechanisms in human cancer. Clin Chim Acta. 2018; 485: 229–233.
- Paraskevopoulou MD, Hatzigeorgiou AG. Analyzing MiRNA-LncRNA Interactions. Methods Mol Biol. 2016; 1402: 271–286.
- Loewen G, Jayawickramarajah J, Zhuo Y, et al. Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol. 2014; 7: 90.
- Zhen Q, Gao LN, Wang RF, et al. LncRNA DANCR Promotes Lung Cancer by Sequestering miR-216a. Cancer Control. 2018; 25(1): 1073274818769849.
- Chen Y, Min L, Ren C, et al. miRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer. PLoS One. 2017; 12(2): e0171751.
- Zhang M, Shi H, Zhang C, et al. MiRNA-621 inhibits the malignant progression of non-small cell lung cancer via targeting SIX4. Eur Rev Med Pharmacol Sci. 2019; 23(11): 4807–4814.
- Li D, Song H, Wu T, et al. MiR-519d-3p suppresses breast cancer cell growth and motility via targeting LIM domain kinase 1. Mol Cell Biochem. 2018; 444(1-2): 169–178.
- Li X, Han X, Yang J, et al. [Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate cancer cells by reducing TRAF4]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2018; 34(1): 16–21.
- Ye Y, Zhao L, Li Q, et al. circ_0007385 served as competing endogenous RNA for miR-519d-3p to suppress malignant behaviors and cisplatin resistance of non-small cell lung cancer cells. Thorac Cancer. 2020; 11(8): 2196–2208.
- Zhao YF, Li L, Li HJ, et al. LncRNA ZFPM2-AS1 aggravates the malignant development of breast cancer via upregulating JMJD6. Eur Rev Med Pharmacol Sci. 2020; 24(21): 11139–11147.
- Wang F, He L, Huangyang P, et al. JMJD6 promotes colon carcinogenesis through negative regulation of p53 by hydroxylation. PLoS Biol. 2014; 12(3): e1001819.
- Zhang Ji, Ni SS, Zhao WL, et al. High expression of JMJD6 predicts unfavorable survival in lung adenocarcinoma. Tumour Biol. 2013; 34(4): 2397–2401.
- Wan J, Xu W, Zhan J, et al. PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6. Nucleic Acids Res. 2016; 44(22): 10662–10675.
- Yang J, Qiu Q, Qian X, et al. Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer. Mol Cancer. 2019; 18(1): 171.
- Chen X, Wang Z, Tong F, et al. lncRNA UCA1 Promotes Gefitinib Resistance as a ceRNA to Target FOSL2 by Sponging miR-143 in Non-small Cell Lung Cancer. Mol Ther Nucleic Acids. 2020; 19: 643–653.
