Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | NSCLC | Primary research

LncRNA KCNQ1OT1 promotes cell proliferation, migration and invasion via regulating miR-129-5p/JAG1 axis in non-small cell lung cancer

Authors: Yan Wang, Lei Zhang, Jiasheng Yang, Ruilin Sun

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Non-small cell lung cancer (NSCLC) is the most deadly cancer worldwide. LncRNA KCNQ1OT1 has been reported to be involved in the progression of various tumors, including NSCLC. However, the precise mechanism of KCNQ1OT1 in NSCLC requires further investigation.

Methods

The expression levels of KCNQ1OT1, miR-129-5p and JAG1 were detected by qRT-PCR or western blot. Kaplan–Meier survival analysis was used to assess the correlation between KCNQ1OT1 expression and the overall survival of NSCLC patients. CCK-8 assay was used to measure cell viability. Cell migration and invasion were detected by transwell assay. The targets of KCNQ1OT1 and miR-129-5p were predicted by bioinformatics, which was confirmed by dual-luciferase reporter assay or pull-down assay.

Results

KCNQ1OT1 expression was significantly enhanced, while miR-129-5p expression was dramatically reduced in NSCLC tissues and cells. Higher KCNQ1OT1 shortened overall survival and was positively associated with tumor stage and lymph node metastasis. KCNQ1OT1 knockdown inhibited proliferation, migration and invasion of NSCLC cells. Inhibition of miR-129-5p attenuated the inhibition of NSCLC cell viability, migration and invasion induced by KCNQ1OT1 knockdown. In addition, JAG1 was confirmed as a target of miR-129-5p. Knockdown of JAG1 reversed the effects of miR-129-5p knockdown on NSCLC progression. KCNQ1OT1 regulated JAG1 expression by sponging miR-129-5p in NSCLC cells.

Conclusion

KCNQ1OT1 induced proliferation, migration and invasion of NSCLC cells by sponging miR-129-5p and regulating JAG1 expression, indicating that KCNQ1OT1 was a therapeutic target for NSCLC.
Appendix
Available only for authorised users
Literature
1.
Kaderbhai C, Tharin Z, Ghiringhelli F. The role of molecular profiling to predict the response to immune checkpoint inhibitors in lung cancer. Cancers (Basel). 2019;11:2.CrossRef
2.
Mukherjee A, Paul M, Mukherjee S. Recent progress in the theranostics application of nanomedicine in lung cancer. Cancers (Basel). 2019;11:5.CrossRef
3.
Hirono T, Jingushi K, Nagata T, Sato M, Minami K, Aoki M, Takeda AH, Umehara T, Egawa H, Nakatsuji Y, et al. MicroRNA-130b functions as an oncomiRNA in non-small cell lung cancer by targeting tissue inhibitor of metalloproteinase-2. Sci Rep. 2019;9(1):6956.CrossRef
4.
Shields EJ, Petracovici AF, Bonasio R. lncRedibly versatile: biochemical and biological functions of long noncoding RNAs. Biochem J. 2019;476(7):1083–104.CrossRef
5.
Zhang L, Dong Y, Wang Y, Gao J, Lv J, Sun J, Li M, Wang M, Zhao Z, Wang J, et al. Long non-coding RNAs in ocular diseases: new and potential therapeutic targets. FEBS J. 2019;286(12):2261–72.CrossRef
6.
Kanduri C. Kcnq1ot1: a chromatin regulatory RNA. Semin Cell Dev Biol. 2011;22(4):343–50.CrossRef
7.
Bian Y, Gao G, Zhang Q, Qian H, Yu L, Yao N, Qian J, Liu B, Qian X. KCNQ1OT1/miR-217/ZEB1 feedback loop facilitates cell migration and epithelial-mesenchymal transition in colorectal cancer. Cancer Biol Ther. 2019;20(6):886–96.CrossRef
8.
Feng W, Wang C, Liang C, Yang H, Chen D, Yu X, Zhao W, Geng D, Li S, Chen Z, et al. The dysregulated expression of KCNQ1OT1 and its interaction with downstream factors miR-145/CCNE2 in breast cancer cells. Cell Physiol Biochem. 2018;49(2):432–46.CrossRef
9.
Zhang S, Ma H, Zhang D, Xie S, Wang W, Li Q, Lin Z, Wang Y. LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling. Cell Death Dis. 2018;9(7):742.CrossRef
10.
Sun H, Li Y, Kong H, Dai S, Qian H. Dysregulation of KCNQ1OT1 promotes cholangiocarcinoma progression via miR-140-5p/SOX4 axis. Arch Biochem Biophys. 2018;658:7–15.CrossRef
11.
Yao Q, Chen Y, Zhou X. The roles of microRNAs in epigenetic regulation. Curr Opin Chem Biol. 2019;51:11–7.CrossRef
12.
Wang S, Chen Y, Yu X, Lu Y, Wang H, Wu F, Teng L. miR-129-5p attenuates cell proliferation and epithelial mesenchymal transition via HMGB1 in gastric cancer. Pathol Res Pract. 2019;215(4):676–82.CrossRef
13.
Shen Q, Jiang Y. LncRNA NNT-AS1 promotes the proliferation, and invasion of lung cancer cells via regulating miR-129-5p expression. Biomed Pharmacother. 2018;105:176–81.CrossRef
14.
Grochowski CM, Loomes KM, Spinner NB. Jagged1 (JAG1): structure, expression, and disease associations. Gene. 2016;576(1 Pt 3):381–4.CrossRef
15.
Tang L, Yang B, Cao X, Li Q, Jiang L, Wang D. MicroRNA-377-3p inhibits growth and invasion through sponging JAG1 in ovarian cancer. Genes Genomics. 2019;41(8):919–26.CrossRef
16.
Wang L, Wang W, Wu Y. MicroRNA-26b acts as an antioncogene and prognostic factor in cervical cancer. Oncol Lett. 2019;17(3):3418–24.PubMedPubMedCentral
17.
Panda AC, Martindale JL, Gorospe M. Affinity pulldown of biotinylated RNA for detection of protein-RNA complexes. Bio Protoc. 2016;6:24.CrossRef
18.
Lu T, Wang Y, Chen D, Liu J, Jiao W. Potential clinical application of lncRNAs in non-small cell lung cancer. Onco Targets Ther. 2018;11:8045–52.CrossRef
19.
Wei MM, Zhou GB. Long non-coding RNAs and Their Roles in Non-small-cell Lung Cancer. Genomics Proteom Bioinform. 2016;14(5):280–8.CrossRef
20.
Li C, Miao R, Zhang J, Qu K, Liu C. Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504. Int J Oncol. 2018;52(5):1603–12.PubMed
21.
Sun X, Xin Y, Wang M, Li S, Miao S, Xuan Y, Wang Y, Lu T, Liu J, Jiao W. Overexpression of long non-coding RNA KCNQ1OT1 is related to good prognosis via inhibiting cell proliferation in non-small cell lung cancer. Thorac Cancer. 2018;9(5):523–31.CrossRef
22.
Dong Z, Yang P, Qiu X, Liang S, Guan B, Yang H, Li F, Sun L, Liu H, Zou G, et al. KCNQ1OT1 facilitates progression of non-small-cell lung carcinoma via modulating miRNA-27b-3p/HSP90AA1 axis. J Cell Physiol. 2019;234(7):11304–14.CrossRef
23.
Yamamura S, Imai-Sumida M, Tanaka Y, Dahiya R. Interaction and cross-talk between non-coding RNAs. Cell Mol Life Sci. 2018;75(3):467–84.CrossRef
24.
Gu LP, Jin S, Xu RC, Zhang J, Geng YC, Shao XY, Qin LB. Long non-coding RNA PCAT-1 promotes tumor progression by inhibiting miR-129-5p in human ovarian cancer. Arch Med Sci. 2019;15(2):513–21.CrossRef
25.
Chen Y, Huang W, Sun W, Zheng B, Wang C, Luo Z, Wang J, Yan W. LncRNA MALAT1 promotes cancer metastasis in osteosarcoma via activation of the PI3K-Akt signaling pathway. Cell Physiol Biochem. 2018;51(3):1313–26.CrossRef
26.
Ma Z, Cai H, Zhang Y, Chang L, Cui Y. MiR-129-5p inhibits non-small cell lung cancer cell stemness and chemoresistance through targeting DLK1. Biochem Biophys Res Commun. 2017;490(2):309–16.CrossRef
27.
Azimi M, Brown NL. Jagged1 protein processing in the developing mammalian lens. Biol Open. 2019;8:3.CrossRef
28.
Chang WH, Ho BC, Hsiao YJ, Chen JS, Yeh CH, Chen HY, Chang GC, Su KY, Yu SL. JAG1 is associated with poor survival through inducing metastasis in lung cancer. PLoS ONE. 2016;11(3):e0150355.CrossRef
Metadata
Title
LncRNA KCNQ1OT1 promotes cell proliferation, migration and invasion via regulating miR-129-5p/JAG1 axis in non-small cell lung cancer
Authors
Yan Wang
Lei Zhang
Jiasheng Yang
Ruilin Sun
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
NSCLC
NSCLC
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01225-8

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Primary research

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

Primary research

High-throughput sequencing identification of differentially expressed microRNAs in metastatic ovarian cancer with experimental validations

Primary research

Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

Primary research

LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2

Primary research

The dual functions of α-tubulin acetylation in cellular apoptosis and autophage induced by tanespimycin in lung cancer cells

Primary research

EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits