Long Non-coding RNAs Are Involved in Alternative Splicing and Promote Cancer Progression

Overview

Journal Br J Cancer

Specialty Oncology

Date 2021 Nov 9

PMID 34750493

Citations 50

Authors

Jiawei Ouyang

Yu Zhong

Yijie Zhang

Liting Yang

Pan Wu

Xiangchan Hou

Fang Xiong

Xiayu Li

Shanshan Zhang

Zhaojian Gong

Yi He

Yanyan Tang

Wenling Zhang

Bo Xiang

Ming Zhou

Jian Ma

Yong Li

Guiyuan Li

Zhaoyang Zeng

Can Guo

Wei Xiong

Affiliations

Soon will be listed here.

Abstract

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.

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References

Liu S, Cheng C . Alternative RNA splicing and cancer. Wiley Interdiscip Rev RNA. 2013; 4(5):547-66. PMC: 4426271. DOI: 10.1002/wrna.1178. View

Bonnal S, Lopez-Oreja I, Valcarcel J . Roles and mechanisms of alternative splicing in cancer - implications for care. Nat Rev Clin Oncol. 2020; 17(8):457-474. DOI: 10.1038/s41571-020-0350-x. View

Wang E, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C . Alternative isoform regulation in human tissue transcriptomes. Nature. 2008; 456(7221):470-6. PMC: 2593745. DOI: 10.1038/nature07509. View

Hu X, Harvey S, Zheng R, Lyu J, Grzeskowiak C, Powell E . The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing. Nat Commun. 2020; 11(1):486. PMC: 6981122. DOI: 10.1038/s41467-020-14304-1. View

Alsafadi S, Houy A, Battistella A, Popova T, Wassef M, Henry E . Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. Nat Commun. 2016; 7:10615. PMC: 4743009. DOI: 10.1038/ncomms10615. View

Jeong S . SR Proteins: Binders, Regulators, and Connectors of RNA. Mol Cells. 2017; 40(1):1-9. PMC: 5303883. DOI: 10.14348/molcells.2017.2319. View

Kedzierska H, Piekielko-Witkowska A . Splicing factors of SR and hnRNP families as regulators of apoptosis in cancer. Cancer Lett. 2017; 396:53-65. DOI: 10.1016/j.canlet.2017.03.013. View

Zhu L, Zhu Y, Dai D, Wang X, Jin H . Epigenetic regulation of alternative splicing. Am J Cancer Res. 2019; 8(12):2346-2358. PMC: 6325479. View

Tan F, Zhao M, Xiong F, Wang Y, Zhang S, Gong Z . N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies. J Exp Clin Cancer Res. 2021; 40(1):146. PMC: 8082653. DOI: 10.1186/s13046-021-01952-4. View

10.

Liu Y, Liu X, Lin C, Jia X, Zhu H, Song J . Noncoding RNAs regulate alternative splicing in Cancer. J Exp Clin Cancer Res. 2021; 40(1):11. PMC: 7789004. DOI: 10.1186/s13046-020-01798-2. View

11.

Fan C, Tang Y, Wang J, Xiong F, Guo C, Wang Y . Role of long non-coding RNAs in glucose metabolism in cancer. Mol Cancer. 2017; 16(1):130. PMC: 5525357. DOI: 10.1186/s12943-017-0699-3. View

12.

Tang Y, He Y, Zhang P, Wang J, Fan C, Yang L . LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis. Mol Cancer. 2018; 17(1):77. PMC: 5885413. DOI: 10.1186/s12943-018-0825-x. View

13.

Wang W, Zhou R, Wu Y, Liu Y, Su W, Xiong W . PVT1 Promotes Cancer Progression via MicroRNAs. Front Oncol. 2019; 9:609. PMC: 6644598. DOI: 10.3389/fonc.2019.00609. View

14.

Wang D, Zeng Z, Zhang S, Xiong F, He B, Wu Y . Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell proliferation through the LOC553103-STMN1 axis. FASEB J. 2020; 34(6):8012-8027. DOI: 10.1096/fj.202000039RR. View

15.

Choudhari R, Sedano M, Harrison A, Subramani R, Lin K, Ramos E . Long noncoding RNAs in cancer: From discovery to therapeutic targets. Adv Clin Chem. 2020; 95:105-147. DOI: 10.1016/bs.acc.2019.08.003. View

16.

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

17.

Bo H, Fan L, Li J, Liu Z, Zhang S, Shi L . High Expression of lncRNA AFAP1-AS1 Promotes the Progression of Colon Cancer and Predicts Poor Prognosis. J Cancer. 2018; 9(24):4677-4683. PMC: 6299385. DOI: 10.7150/jca.26461. View

18.

Lian Y, Xiong F, Yang L, Bo H, Gong Z, Wang Y . Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway. J Exp Clin Cancer Res. 2018; 37(1):253. PMC: 6191894. DOI: 10.1186/s13046-018-0918-9. View

19.

Wei F, Jing Y, He Y, Tang Y, Yang L, Wu Y . Cloning and characterization of the putative AFAP1-AS1 promoter region. J Cancer. 2019; 10(5):1145-1153. PMC: 6400686. DOI: 10.7150/jca.29049. View

20.

Bo H, Fan L, Gong Z, Liu Z, Shi L, Guo C . Upregulation and hypomethylation of lncRNA AFAP1‑AS1 predicts a poor prognosis and promotes the migration and invasion of cervical cancer. Oncol Rep. 2019; 41(4):2431-2439. DOI: 10.3892/or.2019.7027. View