Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

The Role of the LINC01234/miR-433-3p/GRB2 ceRNA Network in NSCLC Cell Malignant Proliferation

Author(s): Wei Wei, Changyong Wang, Jianfeng Zhang, Lele Wang, Lei Wei* and Hairong Huang*

Volume 26, Issue 10, 2023

Published on: 03 November, 2022

Page: [1836 - 1847] Pages: 12

DOI: 10.2174/1386207325666220624093957

Price: $65


Background: Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Dysregulation of lncRNAs leads to NSCLC progression.

Objective: This study aims to explore the regulatory mechanism of lncRNA LINC01234 in NSCLC.

Materials and Methods: LINC01234 expression in NSCLC cells was determined. Cell proliferation was detected using CCK-8, colony formation, and EDU assays after transfection of siRNA LINC01234 into H1299 cells and transfection of pcDNA3.1-LINC01234 into H1975 cells. Subcellular localization of LINC01234 was predicted and the binding relations between LINC01234 and miR-433-3p as well as miR-433-3p and GRB2 were verified. The expression levels of miR-433-3p and GRB2 in NSCLC cells were determined. Joint experiments of miR-433-3p inhibitor + si- LINC01234-1 or oe-GRB2 + si-LINC01234-1 were conducted to verify the role of miR-433-3p and GRB2 in NSCLC cell malignant proliferation.

Results: LINC01234 was abundantly expressed in NSCLC cells. LINC01234 silencing reduced NSCLC cell proliferation while LINC01234 overexpression enhanced cell proliferation. LINC01234 competitively bound to miR-433-3p and miR-433-3p directly targeted GRB2. miR- 433-3p knockdown or GRB2 overexpression counteracted the repressive effect of LINC01234 silencing on NSCLC cell malignant proliferation.

Conclusion: LINC01234 competitively bound to miR-433-3p and promoted GRB2 transcription to augment NSCLC cell malignant proliferation.

Keywords: Non-small cell lung cancer, LINC01234, microRNA-433-3p, GRB2, malignant proliferation, competing endogenous RNA, EDU, colony formation.

Graphical Abstract
Majeed, U.; Manochakian, R.; Zhao, Y.; Lou, Y. Targeted therapy in advanced non-small cell lung cancer: Current advances and future trends. J. Hematol. Oncol., 2021, 14(1), 108.
[] [PMID: 34238332]
Rivera, G.A.; Wakelee, H. Lung cancer in never smokers. Adv. Exp. Med. Biol., 2016, 893, 43-57.
[] [PMID: 26667338]
Ostrowski, M.; Marjański, T.; Rzyman, W. Low-dose computed tomography screening reduces lung cancer mortality. Adv. Med. Sci., 2018, 63(2), 230-236.
[] [PMID: 29425790]
VanderLaan, P.A.; Roy-Chowdhuri, S. Current and future trends in non-small cell lung cancer biomarker testing: The American experience. Cancer Cytopathol., 2020, 128(9), 629-636.
[] [PMID: 32885913]
Herbst, R.S.; Morgensztern, D.; Boshoff, C. The biology and management of non-small cell lung cancer. Nature, 2018, 553(7689), 446-454.
[] [PMID: 29364287]
Chen, J.; Wang, R.; Zhang, K.; Chen, L.B. Long non-coding RNAs in non-small cell lung cancer as biomarkers and therapeutic targets. J. Cell. Mol. Med., 2014, 18(12), 2425-2436.
[] [PMID: 25297942]
Jiang, X.; Zhu, Q.; Wu, P.; Zhou, F.; Chen, J. Upregulated long noncoding RNA LINC01234 predicts unfavorable prognosis for colorectal cancer and negatively correlates with KLF6 expression. Ann. Lab. Med., 2020, 40(2), 155-163.
[] [PMID: 31650732]
Chen, Z.; Chen, X.; Lu, B.; Gu, Y.; Chen, Q.; Lei, T.; Nie, F.; Gu, J.; Huang, J.; Wei, C.; Sun, M.; Wang, Z. Up-regulated LINC01234 promotes non-small-cell lung cancer cell metastasis by activating VAV3 and repressing BTG2 expression. J. Hematol. Oncol., 2020, 13(1), 7.
[] [PMID: 31959200]
Chen, X.; Chen, Z.; Yu, S.; Nie, F.; Yan, S.; Ma, P.; Chen, Q.; Wei, C.; Fu, H.; Xu, T.; Ren, S.; Sun, M.; Wang, Z. Long noncoding RNA LINC01234 functions as a competing endogenous RNA to regulate CBFB expression by sponging miR-204-5p in gastric cancer. Clin. Cancer Res., 2018, 24(8), 2002-2014.
[] [PMID: 29386218]
Chan, J.J.; Tay, Y. Noncoding RNA: RNA regulatory networks in cancer. Int. J. Mol. Sci., 2018, 19(5), E1310.
[] [PMID: 29702599]
Feng, B.; Zhang, K.; Wang, R.; Chen, L. Non-small-cell lung cancer and miRNAs: Novel biomarkers and promising tools for treatment. Clin. Sci. (Lond.), 2015, 128(10), 619-634.
[] [PMID: 25760961]
Sun, S.; Wang, X.; Xu, X.; Di, H.; Du, J.; Xu, B.; Wang, Q.; Wang, J. MiR-433-3p suppresses cell growth and enhances chemosensitivity by targeting CREB in human glioma. Oncotarget, 2017, 8(3), 5057-5068.
[] [PMID: 27926502]
Weng, L.; Qiu, K.; Gao, W.; Shi, C.; Shu, F. LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP. BMC Pulm. Med., 2020, 20(1), 213.
[] [PMID: 32787827]
Ijaz, M.; Wang, F.; Shahbaz, M.; Jiang, W.; Fathy, A.H.; Nesa, E.U. The role of Grb2 in cancer and peptides as Grb2 antagonists. Protein Pept. Lett., 2018, 24(12), 1084-1095.
[] [PMID: 29173143]
Jiang, W.; Wei, K.; Pan, C.; Li, H.; Cao, J.; Han, X.; Tang, Y.; Zhu, S.; Yuan, W.; He, Y.; Xia, Y.; Chen, L.; Chen, Y. MicroRNA-1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non-small-cell lung cancer. Cell Prolif., 2018, 51(6), e12502.
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nuc. Acids Res., 2014, 42(Database issue), D92-97.
Mas-Ponte, D.; Carlevaro-Fita, J.; Palumbo, E.; Hermoso Pulido, T.; Guigo, R.; Johnson, R. LncATLAS database for subcellular localization of long noncoding RNAs. RNA, 2017, 23(7), 1080-1087.
Loher, P.; Rigoutsos, I. Interactive exploration of RNA22 microRNA target predictions. Bioinformatics, 2012, 28(24), 3322-3323.
Paraskevopoulou, M.D.; Georgakilas, G.; Kostoulas, N.; Reczko, M.; Maragkakis, M.; Dalamagas, T.M.; Hatzigeorgiou, A.G. DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs. Nuc. Acids Res., 2013, 41(Database issue), D239-245.
Miao, Y.R.; Liu, W.; Zhang, Q.; Guo, A.Y. lncRNASNP2: an updated database of functional SNPs and mutations in human and mouse lncRNAs. Nuc. Acids Res., 2018, 46(D1), D276-D280.
Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. Elife, 2015, 4.
Hsu, S.D.; Lin, F.M.; Wu, W.Y.; Liang, C.; Huang, W.C.; Chan, W.L.; Tsai, W.T.; Chen, G.Z.; Lee, C.J.; Chiu, C.M.; Chien, C.H.; Wu, M.C.; Huang, C.Y.; Tsou, A.P.; Huang, H.D. miRTar-Base: a database curates experimentally validated microRNA-target interactions. Nuc. Acids Res., 2011, 39(Database issue), D163-169.
Yuan, M.; Huang, L.L.; Chen, J.H.; Wu, J.; Xu, Q. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct. Target. Ther., 2019, 4(1), 61.
[] [PMID: 31871778]
Cantor, J.R.; Sabatini, D.M. Cancer cell metabolism: one hallmark, many faces. Cancer Discov., 2012, 2(10), 881-898.
[] [PMID: 23009760]
Chen, Z.; Chen, X.; Lei, T.; Gu, Y.; Gu, J.; Huang, J.; Lu, B.; Yuan, L.; Sun, M.; Wang, Z. Integrative analysis of NSCLC identifies LINC01234 as an oncogenic lncRNA that interacts with HNRNPA2B1 and regulates miR-106b biogenesis. Mol. Ther., 2020, 28(6), 1479-1493.
[] [PMID: 32246902]
Ginn, L.; Shi, L.; Montagna, M.; Garofalo, M. LncRNAs in non-small-cell lung cancer. Noncoding RNA, 2020, 6(3), E25.
[] [PMID: 32629922]
Liao, X.; Zhan, W.; Zhang, J.; Cheng, Z.; Li, L.; Tian, T.; Yu, L.; Li, R. Long noncoding RNA LINC01234 promoted cell proliferation and invasion via miR-1284/TRAF6 axis in colorectal cancer. J. Cell. Biochem., 2020, 121(10), 4295-4309.
[] [PMID: 31904146]
Chen, Y.; Zhao, H.; Li, H.; Feng, X.; Tang, H.; Qiu, C.; Zhang, J.; Fu, B. LINC01234/MicroRNA-31-5p/MAGEA3 axis mediates the proliferation and chemoresistance of hepatocellular carcinoma cells. Mol. Ther. Nucleic Acids, 2020, 19, 168-178.
[] [PMID: 31838274]
Xie, J.J.; Guo, Q.Y.; Jin, J.Y.; Jin, D. SP1-mediated overexpression of lncRNA LINC01234 as a ceRNA facilitates non-small-cell lung cancer progression via regulating OTUB1. J. Cell. Physiol., 2019, 234(12), 22845-22856.
[] [PMID: 31106421]
Karreth, F.A.; Pandolfi, P.P. ceRNA cross-talk in cancer: When cebling rivalries go awry. Cancer Discov., 2013, 3(10), 1113-1121.
[] [PMID: 24072616]
Petrek, H.; Yu, A.M. MicroRNAs in non-small cell lung cancer: Gene regulation, impact on cancer cellular processes, and therapeutic potential. Pharmacol. Res. Perspect., 2019, 7(6), e00528.
[] [PMID: 31859460]
Liu, D.; Jian, X.; Xu, P.; Zhu, R.; Wang, Y. Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis. BMC Cancer, 2020, 20(1), 107.
[] [PMID: 32041570]
Zhou, X.; Liu, K.; Cui, J.; Xiong, J.; Wu, H.; Peng, T.; Guo, Y. Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. J. Exp. Clin. Cancer Res., 2021, 40(1), 124.
[] [PMID: 33832516]
Hong, W.; Ying, H.; Lin, F.; Ding, R.; Wang, W.; Zhang, M. lncRNA LINC00460 silencing represses EMT in colon cancer through down-regulation of ANXA2 via upregulating miR-433-3p. Mol. Ther. Nucleic Acids, 2020, 19, 1209-1218.
[] [PMID: 32069703]
Liu, X.; Huang, S.; Guan, Y.; Zhang, Q. Long noncoding RNA OSER1-AS1 promotes the malignant properties of non-small cell lung cancer by sponging microRNA-433-3p and thereby increasing Smad2 expression. Oncol. Rep., 2020, 44(2), 599-610.
[] [PMID: 32627026]
Shi, Q.; Wang, Y.; Mu, Y.; Wang, X.; Fan, Q. MiR-433-3p inhibits proliferation and invasion of esophageal squamous cell carcinoma by targeting GRB2. Cell. Physiol. Biochem., 2018, 46(5), 2187-2196.
[] [PMID: 29730656]
Ma, Q.; Song, J.; Ma, H.; Gao, K.; Yang, Y.; He, N. Synergistic anticancer effect of Grb2 and ITGA1 on cancer cells highly expressing Grb2 through suppressing ERK phosphorylation. Int. J. Clin. Exp. Pathol., 2019, 12(1), 182-189.
[PMID: 31933732]
Ren, X.; Xu, N.; Zhang, Y.; Wang, T. Downregulation of long non-coding RNA ZXF1 restricts cell survival by targeting miR-634-GRB2 in lung adenocarcinoma. Acta Biochim. Pol., 2020, 67(1), 31-39.
[] [PMID: 32160453]
Chen, Y.; Wu, J.; Yan, H.; Cheng, Y.; Wang, Y.; Yang, Y.; Deng, M.; Che, X.; Hou, K.; Qu, X.; Zou, D.; Liu, Y.; Zhang, Y.; Hu, X. Lymecycline reverses acquired EGFR-TKI resistance in non-small-cell lung cancer by targeting GRB2. Pharmacol. Res., 2020, 159, 105007.
[] [PMID: 32561477]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy