LncRNA LINC01134 Contributes to Radioresistance in Hepatocellular Carcinoma by Regulating DNA Damage Response MAPK Signaling Pathway

Overview

Journal Front Pharmacol

Date 2022 Feb 17

PMID 35173610

Authors

Zhiyi Wang

Xinxing Wang

Zhonghou Rong

Longfei Dai

Chengkun Qin

Shikang Wang

Wenmao Geng

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is a highly mortal cancer that could be treated by radiotherapy. DNA damage response (DDR) is a vital factor affecting cancer development after radiotherapy. Long non-coding RNAs (lncRNAs) have been revealed to regulate DNA damage response and repair in cancer cells. Nevertheless, the function of long intergenic non-protein coding RNA 1134 (LINC01134) has not been explored in DDR. In this study, we targeted digging into the function of LINC01134 in DDR and exploring the underlying mechanism in HCC cells. RT-qPCR was employed to measure LINC01134 expression, and we found LINC01134 was significantly upregulated in HCC cells. Functional analysis suggested that LINC01134 depletion attenuated radioresistance of HCC cells by facilitating DNA damage. assays demonstrated LINC01134 depletion hindered HCC tumor growth. Mechanism assays unveiled LINC01134 sequestered microRNA-342-3p (miR-342-3p) and recruited insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) protein to modulate mitogen-activated protein kinase 1 (MAPK1) expression, consequently activating MAPK signaling pathway. Rescue assays validated the LINC01134/miR-342-3p/MAPK1 axis in the radio-resistant HCC cells. In conclusion, LINC01134 might be identified to be a useful biomarker for the therapy of HCC.

Citing Articles

LINC01134 Directly Binds and Regulates SLC1A5 Stability to Promotes Colorectal Cancer Progression.

Yao L, Wu J, Wang X, Wang N J Cancer. 2024; 15(18):6135-6147.

PMID: 39440055 PMC: 11493009. DOI: 10.7150/jca.100147.

Therapeutic effects of paeonol on non‑small cell lung cancer cells via regulation of the MAPK pathway.

Gan W, Chen C, Huang M, Li Y Oncol Lett. 2024; 28(6):560.

PMID: 39372664 PMC: 11450707. DOI: 10.3892/ol.2024.14693.

Identification and validation of a five-necroptosis-related lncRNAs signature for prognostic prediction in hepatocellular carcinoma.

Chen H, Hou G, Lan T, Xue S, Xu L, Feng Q Heliyon. 2024; 10(18):e37403.

PMID: 39309864 PMC: 11415698. DOI: 10.1016/j.heliyon.2024.e37403.

DNA damage response-related ncRNAs as regulators of therapy resistance in cancer.

Gao Z, Luan X, Wang X, Han T, Li X, Li Z Front Pharmacol. 2024; 15:1390300.

PMID: 39253383 PMC: 11381396. DOI: 10.3389/fphar.2024.1390300.

Construction and validation of a prognostic signature for mucinous colonic adenocarcinoma based on N7-methylguanosine-related long non-coding RNAs.

Gao Y, Ren J, Chen K, Guan G J Gastrointest Oncol. 2024; 15(1):203-219.

PMID: 38482248 PMC: 10932661. DOI: 10.21037/jgo-23-980.

References

He Y, Jing Y, Wei F, Tang Y, Yang L, Luo J . Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma. Cell Death Dis. 2018; 9(2):235. PMC: 5833381. DOI: 10.1038/s41419-018-0265-y. View

Gao Y, Zhang S, Wang Z, Liao J . Down-regulation of miR-342-3p in hepatocellular carcinoma tissues and its prognostic significance. Eur Rev Med Pharmacol Sci. 2017; 21(9):2098-2102. View

Brinegar A, Cooper T . Roles for RNA-binding proteins in development and disease. Brain Res. 2016; 1647:1-8. PMC: 5003702. DOI: 10.1016/j.brainres.2016.02.050. View

Li B, Mao R, Liu C, Zhang W, Tang Y, Guo Z . LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. Life Sci. 2018; 197:122-129. DOI: 10.1016/j.lfs.2018.02.006. View

Zhang Y, He Q, Hu Z, Feng Y, Fan L, Tang Z . Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer. Nat Struct Mol Biol. 2016; 23(6):522-30. PMC: 4927085. DOI: 10.1038/nsmb.3211. View

Rong Z, Wang Z, Wang X, Qin C, Geng W . Molecular interplay between linc01134 and YY1 dictates hepatocellular carcinoma progression. J Exp Clin Cancer Res. 2020; 39(1):61. PMC: 7146959. DOI: 10.1186/s13046-020-01551-9. View

Wu M, Tong C, Yan W, To K, Cho W . The RNA Binding Protein HuR: A Promising Drug Target for Anticancer Therapy. Curr Cancer Drug Targets. 2018; 19(5):382-399. DOI: 10.2174/1568009618666181031145953. View

Simon Y, Kessler S, Bohle R, Haybaeck J, Kiemer A . The insulin-like growth factor 2 (IGF2) mRNA-binding protein p62/IGF2BP2-2 as a promoter of NAFLD and HCC?. Gut. 2013; 63(5):861-3. PMC: 3995267. DOI: 10.1136/gutjnl-2013-305736. View

Song J, Tian S, Yu L, Xing Y, Yang Q, Duan X . AC-Caps: Attention Based Capsule Network for Predicting RBP Binding Sites of LncRNA. Interdiscip Sci. 2020; 12(4):414-423. DOI: 10.1007/s12539-020-00379-3. View

10.

Dong J, Teng F, Guo W, Yang J, Ding G, Fu Z . lncRNA SNHG8 Promotes the Tumorigenesis and Metastasis by Sponging miR-149-5p and Predicts Tumor Recurrence in Hepatocellular Carcinoma. Cell Physiol Biochem. 2018; 51(5):2262-2274. DOI: 10.1159/000495871. View

11.

Lim L, Wong S, Huang F, Lim S, Chong S, Ooi L . Roles and Regulation of Long Noncoding RNAs in Hepatocellular Carcinoma. Cancer Res. 2019; 79(20):5131-5139. DOI: 10.1158/0008-5472.CAN-19-0255. View

12.

Wu X, Sui Z, Zhang H, Wang Y, Yu Z . Integrated Analysis of lncRNA-Mediated ceRNA Network in Lung Adenocarcinoma. Front Oncol. 2020; 10:554759. PMC: 7523091. DOI: 10.3389/fonc.2020.554759. View

13.

Taiana E, Favasuli V, Ronchetti D, Todoerti K, Pelizzoni F, Manzoni M . Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma. Leukemia. 2019; 34(1):234-244. DOI: 10.1038/s41375-019-0542-5. View

14.

Wang H, Ke J, Guo Q, Barnabo Nampoukime K, Yang P, Ma K . Long non-coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK1 axis. J Cell Mol Med. 2018; 22(12):5862-5876. PMC: 6237590. DOI: 10.1111/jcmm.13856. View

15.

Yao Z, Zhang Y, Xu D, Zhou X, Peng P, Pan Z . Research Progress on Long Non-Coding RNA and Radiotherapy. Med Sci Monit. 2019; 25:5757-5770. PMC: 6690404. DOI: 10.12659/MSM.915647. View

16.

Sun J, Zhu Z, Li W, Shen M, Cao C, Sun Q . UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation. J Exp Clin Cancer Res. 2020; 39(1):222. PMC: 7576867. DOI: 10.1186/s13046-020-01734-4. View

17.

Wang Y, Wang Y, Luo W, Song X, Huang L, Xiao J . Roles of long non-coding RNAs and emerging RNA-binding proteins in innate antiviral responses. Theranostics. 2020; 10(20):9407-9424. PMC: 7415804. DOI: 10.7150/thno.48520. View

18.

Wen Z, Lian L, Ding H, Hu Y, Xiao Z, Xiong K . LncRNA ANCR promotes hepatocellular carcinoma metastasis through upregulating HNRNPA1 expression. RNA Biol. 2019; 17(3):381-394. PMC: 6999620. DOI: 10.1080/15476286.2019.1708547. View

19.

Ma H, Yuan L, Li W, Xu K, Yang L . The LncRNA H19/miR-193a-3p axis modifies the radio-resistance and chemotherapeutic tolerance of hepatocellular carcinoma cells by targeting PSEN1. J Cell Biochem. 2018; 119(10):8325-8335. DOI: 10.1002/jcb.26883. View

20.

Ye Y, Guo J, Xiao P, Ning J, Zhang R, Liu P . Macrophages-induced long noncoding RNA H19 up-regulation triggers and activates the miR-193b/MAPK1 axis and promotes cell aggressiveness in hepatocellular carcinoma. Cancer Lett. 2019; 469:310-322. DOI: 10.1016/j.canlet.2019.11.001. View