Top

BMC Pulmonary Medicine

Published in:

Open Access 01-12-2020 | Research article

LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression

Authors: Tao Wang, Ruiren Zhai, Xiuhua Lv, Ke Wang, Junqing Xu

Published in: BMC Pulmonary Medicine | Issue 1/2020

Abstract

Background

Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn’t been mentioned in previous studies on cancer development. Therefore, it’s important to define the potential function of LINC02418 in LAD.

Methods

Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays.

Results

High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells.

Conclusions

LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD.

Available only for authorised users

Chou J, Wang B, Zheng T, Li X, Zheng L, Hu J, Zhang Y, Xing Y, Xi T. MALAT1 induced migration and invasion of human breast cancer cells by competitively binding miR-1 with cdc42. Biochem Biophys Res Commun. 2016;472(1):262–9.PubMed

Wei X, Zhang K, Qin H, Zhu J, Qin Q, Yu Y, Wang H. GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma. BMC Cancer. 2018;18(1):600.PubMedPubMedCentral

Janku F, Stewart DJ, Kurzrock R. Targeted therapy in non-small-cell lung cancer--is it becoming a reality? Nat Rev Clin Oncol. 2010;7(7):401–14.PubMed

Ihle NT, Byers LA, Kim ES, Saintigny P, Lee JJ, Blumenschein GR, Tsao A, Liu S, Larsen JE, Wang J, et al. Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. J Natl Cancer Inst. 2012;104(3):228–39.PubMedPubMedCentral

Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12(2):175–80.PubMed

Morgensztern D, Campo MJ, Dahlberg SE, Doebele RC, Garon E, Gerber DE, Goldberg SB, Hammerman PS, Heist RS, Hensing T, et al. Molecularly targeted therapies in non-small-cell lung cancer annual update 2014. J Thorac Oncol. 2015;10(1 Suppl 1):S1–63.PubMedPubMedCentral

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.PubMed

Zheng Y, Liu L, Shukla GC. A comprehensive review of web-based non-coding RNA resources for cancer research. Cancer Lett. 2017;407:1–8.PubMed

Gomes CC, de Sousa SF, Calin GA, Gomez RS. The emerging role of long noncoding RNAs in oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123(2):235–41.PubMed

10.

Zhao L, Wu D, Sang M, Xu Y, Liu Z, Wu Q. Stachydrine ameliorates isoproterenol-induced cardiac hypertrophy and fibrosis by suppressing inflammation and oxidative stress through inhibiting NF-kappaB and JAK/STAT signaling pathways in rats. Int Immunopharmacol. 2017;48:102–9.PubMed

11.

Peng Z, Wang J, Shan B, Li B, Peng W, Dong Y, Shi W, Zhao W, He D, Duan M, et al. The long noncoding RNA LINC00312 induces lung adenocarcinoma migration and vasculogenic mimicry through directly binding YBX1. Mol Cancer. 2018;17(1):167.PubMedPubMedCentral

12.

Hu Y, Ma Z, He Y, Liu W, Su Y, Tang Z. LncRNA-SNHG1 contributes to gastric cancer cell proliferation by regulating DNMT1. Biochem Biophys Res Commun. 2017;491(4):926–31.PubMed

13.

Jing H, Qu X, Liu L, Xia H. A Novel Long Noncoding RNA (lncRNA), LL22NC03-N64E9.1, Promotes the Proliferation of Lung Cancer Cells and is a Potential Prognostic Molecular Biomarker for Lung Cancer. Med Sci Monit. 2018;24:4317–23.PubMedPubMedCentral

14.

Hao Y, Yang X, Zhang D, Luo J, Chen R. Long noncoding RNA LINC01186, regulated by TGF-beta/SMAD3, inhibits migration and invasion through epithelial-Mesenchymal-transition in lung cancer. Gene. 2017;608:1–12.PubMed

15.

Pan C, Yao G, Liu B, Ma T, Xia Y, Wei K, Wang J, Xu J, Chen L, Chen Y. Long noncoding RNA FAL1 promotes cell proliferation, invasion and epithelial-Mesenchymal transition through the PTEN/AKT signaling Axis in non-small cell lung Cancer. Cell Physiol Biochem. 2017;43(1):339–52.PubMed

16.

Dong HX, Wang R, Jin XY, Zeng J, Pan J. LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa-mir-22-3p. J Cell Physiol. 2018;233(5):4126–36.PubMed

17.

Zhou W, Chen X, Hu Q, Chen X, Chen Y, Huang L. Galectin-3 activates TLR4/NF-kappaB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression. BMC Cancer. 2018;18(1):580.PubMedPubMedCentral

18.

Qin J, Ning H, Zhou Y, Hu Y, Yang L, Huang R. LncRNA MIR31HG overexpression serves as poor prognostic biomarker and promotes cells proliferation in lung adenocarcinoma. Biomed Pharmacother. 2018;99:363–8.PubMed

19.

Ma T, Ma H, Zou Z, He X, Liu Y, Shuai Y, Xie M, Zhang Z. The long Intergenic noncoding RNA 00707 promotes lung adenocarcinoma cell proliferation and migration by regulating Cdc42. Cell Physiol Biochem. 2018;45(4):1566–80.PubMed

20.

Deng J, Deng H, Liu C, Liang Y, Wang S. Long non-coding RNA OIP5-AS1 functions as an oncogene in lung adenocarcinoma through targeting miR-448/Bcl-2. Biomed Pharmacother. 2018;98:102–10.PubMed

21.

Li S, Ma F, Jiang K, Shan H, Shi M, Chen B. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 promotes lung adenocarcinoma by directly interacting with specificity protein 1. Cancer Sci. 2018;109(5):1346–56.PubMedPubMedCentral

22.

Li XY, Zhou LY, Luo H, Zhu Q, Zuo L, Liu GY, Feng C, Zhao JY, Zhang YY, Li X. The long noncoding RNA MIR210HG promotes tumor metastasis by acting as a ceRNA of miR-1226-3p to regulate mucin-1c expression in invasive breast cancer. Aging. 2019;11(15):5646–65.PubMedPubMedCentral

23.

Wang L, Luan T, Zhou S, Lin J, Yang Y, Liu W, Tong X, Jiang W. LncRNA HCP5 promotes triple negative breast cancer progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p. Cancer Med. 2019;8(9):4389–403.PubMedPubMedCentral

24.

Wang W, Yuan X, Xu A, Zhu X, Zhan Y, Wang S, Liu M. Human cancer cells suppress behaviors of endothelial progenitor cells through miR-21 targeting IL6R. Microvasc Res. 2018;120:21–8.PubMed

25.

Jin K, Zhao W, Xie X, Pan Y, Wang K, Zhang H. MiR-520b restrains cell growth by targeting HDAC4 in lung cancer. Thoracic cancer. 2018;9(10):1249–54.PubMedPubMedCentral

26.

Chen Z, Hu X, Wu Y, Cong L, He X, Lu J, Feng J, Liu D. Long non-coding RNA XIST promotes the development of esophageal cancer by sponging miR-494 to regulate CDK6 expression. Biomed Pharmacother. 2019;109:2228–36.PubMed

27.

Kadara H, Kabbout M, Wistuba II. Pulmonary adenocarcinoma: a renewed entity in 2011. Respirology (Carlton). 2012;17(1):50–65.

28.

Stahel RA. Adenocarcinoma, a molecular perspective. Ann Oncol. 2007;18(Suppl 9):ix147–9.PubMed

29.

Teglasi V, Reiniger L, Fabian K, Pipek O, Csala I, Bago AG, Varallyai P, Vizkeleti L, Rojko L, Timar J, et al. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis. Neuro-oncology. 2017;19(8):1058–67.PubMedPubMedCentral

30.

Liu D, Vokes NI, Van Allen EM. Toward molecularly driven precision medicine in lung adenocarcinoma. Cancer Discov. 2017;7(6):555–7.PubMedPubMedCentral

31.

Masuda T, Hattori N, Hamada A, Iwamoto H, Ohshimo S, Kanehara M, Ishikawa N, Fujitaka K, Haruta Y, Murai H, et al. Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol. 2011;67(6):1465–9.PubMed

32.

Gottfried M, Bennouna J, Bondarenko I, Douillard JY, Heigener DF, Krzakowski M, Mellemgaard A, Novello S, Orlov S, Summers Y, et al. Efficacy and safety of Nintedanib plus Docetaxel in patients with advanced lung adenocarcinoma: complementary and exploratory analyses of the phase III LUME-lung 1 study. Target Oncol. 2017;12(4):475–85.PubMed

33.

Bittner N, Ostoros G, Geczi L. New treatment options for lung adenocarcinoma--in view of molecular background. Pathol Oncol Res. 2014;20(1):11–25.PubMed

34.

Zhou J, Xiao H, Yang X, Tian H, Xu Z, Zhong Y, Ma L, Zhang W, Qiao G, Liang J. Long noncoding RNA CASC9.5 promotes the proliferation and metastasis of lung adenocarcinoma. Sci Rep. 2018;8(1):37.PubMedPubMedCentral

35.

Li Z, Hou P, Fan D, Dong M, Ma M, Li H, Yao R, Li Y, Wang G, Geng P, et al. The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer. Cell Death Differ. 2017;24(1):59–71.PubMed

36.

D'Angelo B, Benedetti E, Cimini A, Giordano A. MicroRNAs: a puzzling tool in Cancer diagnostics and therapy. Anticancer Res. 2016;36(11):5571–5.PubMed

37.

Cui J, Zhou B, Ross SA, Zempleni J. Nutrition, microRNAs, and Human Health. Adv Nutr (Bethesda). 2017;8(1):105–12.

38.

Cheng Y, Ji R, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C. MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am J Pathol. 2007;170(6):1831–40.PubMedPubMedCentral

39.

Djuranovic S, Nahvi A, Green R. miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science. 2012;336(6078):237–40.PubMedPubMedCentral

40.

Yu FY, Tu Y, Deng Y, Guo C, Ning J, Zhu Y, Lv X, Ye H. MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2. Cancer Biol Ther. 2016;17(11):1149–57.PubMedPubMedCentral

41.

Kong Q, Han J, Deng H, Wu F, Guo S, Ye Z. miR-431-5p alters the epithelial-to-mesenchymal transition markers by targeting UROC28 in hepatoma cells. Onco Targets Ther. 2018;11:6489–503.PubMedPubMedCentral

42.

Li FF, Xing C, Wu LL, Xue F. MiR-205 enhances cisplatin sensitivity of glioma cells by targeting E2F1. Eur Rev Med Pharmacol Sci. 2018;22(2):299–306.PubMed

43.

Wei G, Xu Y, Peng T, Yan J. miR-133 involves in lung adenocarcinoma cell metastasis by targeting FLOT2. Artif Cells Nanomed Biotechnol. 2018;46(2):224–30.PubMed

44.

Li B, Meng YQ, Li Z, Yin C, Lin JP, Zhu DJ, Zhang SB. MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma. Artif Cells Nanomed Biotechnol. 2019;47(1):3286–96.PubMed

45.

Zhang N, Li Y, Zheng Y, Zhang L, Pan Y, Yu J, Yang M. miR-608 and miR-4513 significantly contribute to the prognosis of lung adenocarcinoma treated with EGFR-TKIs. Lab Invest. 2019;99(4):568–76.PubMed

46.

Wang A, Bao Y, Wu Z, Zhao T, Wang D, Shi J, Liu B, Sun S, Yang F, Wang L, et al. Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer. Cell Death Dis. 2019;10(3):154.PubMedPubMedCentral

47.

Ji N, Wang Y, Bao G, Yan J, Ji S. LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ. Pathol Res Pract. 2019;215(4):668–75.PubMed

48.

Song B, Du J, Song DF, Ren JC, Feng Y. Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer. Biol Res. 2018;51(1):44.PubMedPubMedCentral

49.

Qi X, Zhang DH, Wu N, Xiao JH, Wang X, Ma W. ceRNA in cancer: possible functions and clinical implications. J Med Genet. 2015;52(10):710–8.PubMed

50.

Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? Cell. 2011;146(3):353–8.PubMedPubMedCentral

51.

Wang H, Huo X, Yang XR, He J, Cheng L, Wang N, Deng X, Jin H, Wang N, Wang C, et al. STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 2017;16(1):136.PubMedPubMedCentral

52.

Lei H, Gao Y, Xu X. LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim Biophys Sin. 2017;49(7):588–97.PubMed

53.

Jiao C, Song Z, Chen J, Zhong J, Cai W, Tian S, Chen S, Yi Y, Xiao Y. lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer. Oncol Rep. 2016;36(5):2960–6.PubMed

Title: LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression
Authors: Tao Wang
Ruiren Zhai
Xiuhua Lv
Ke Wang
Junqing Xu
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-020-01229-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Correction to: Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation

Clinical and lung function outcomes in a cohort of children with severe asthma

Risk factors associated with the detection of pulmonary emphysema in older asymptomatic respiratory subjects

Correction to: Silent hypoxia: higher NO in red blood cells of COVID-19 patients

Multiple intraventricular metastases from lung adenocarcinoma with EGFR G719X mutation: a case report

Retropharyngeal abscess in a post-lung transplant cystic fibrosis patient with prior cervical fusion: a case study

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page