LINC00963 Confers Oncogenic Properties in Glioma by Regulating the MiR-506/BCAT1 Axis

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Apr 11

PMID 32273770

Citations 7

Authors

Feng Ye

RongHua Xu

YuanHong Ge

Yi Zheng

Xiaowei Liu

Pingfu Deng

Xuejun Xu

Affiliations

Soon will be listed here.

Abstract

Background: Glioma is a prevalent disease of the central nervous system with a high incidence and mortality rate. Many long noncoding RNAs (lncRNAs) have been determined to be critical regulators of glioma oncogenesis. However, the function and mechanism of LINC00963 in glioma have not been fully elucidated.

Methods: The expression level of RNA was determined by qRT-PCR, and the protein level was determined by Western blot analysis. A luciferase activity assay was conducted to verify the interaction between miRNA and lncRNA or the target gene. The proliferation, cell cycle distribution, invasion, and migration were evaluated by MTT, EdU, flow cytometry, wound-healing and Transwell invasion assays, respectively. In vivo tumor growth was evaluated in a xenograft nude mouse model.

Results: We found that LINC00963 was upregulated in glioma cells and tissues and associated with the poor prognosis of patients with glioma. Ectopic expression of LINC00963 promoted cell proliferation, cell cycle progression, migration, and invasion in vitro and tumorigenesis in vivo. Mechanistically, the results of luciferase activity and RNA pulldown assays validated that LINC00963 could act as a molecular sponge of miR-506. Reciprocal repression was found between LINC00963 and miR-506. In addition, BCAT1 was identified as a target of miR-506, and both the mRNA and protein levels of BCAT1 were reduced by miR-506. In tumor tissues, the expression of BCAT1 was negatively and positively correlated with miR-506 and LINC00963 expression, respectively. The reintroduction of BCAT1 in glioma cells abolished the tumor suppressive function of miR-506 by promoting cell viability and motility. The upregulated LINC00963 and BCAT1 were associated with the aggressive phenotypes of tumors.

Conclusion: Our data revealed that LINC00963 confers oncogenic function in the progression of glioma and that the LINC00963/miR-506/BCAT1 axis may be a novel mechanism and therapeutic strategy for this disease.

Citing Articles

LINC00963 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma by Interacting with miR-10a to Upregulate SKA1 Expression.

Hu D, Ma A, Lu H, Gao Z, Yu Y, Fan J Appl Biochem Biotechnol. 2024; 196(10):7219-7232.

PMID: 38507172 DOI: 10.1007/s12010-024-04897-4.

LncRNA PSMB8-AS1 increases glioma malignancy via the miR-382-3p/BCAT1 axis.

Liu H, Zhang J, Li J, Cao X, Yu K, Xia X Transl Oncol. 2024; 39:101806.

PMID: 38235619 PMC: 10628860. DOI: 10.1016/j.tranon.2023.101806.

The role of branched-chain aminotransferase 1 in driving glioblastoma cell proliferation and invasion varies with tumor subtype.

Fala M, Ros S, Sawle A, Rao J, Tsyben A, Tronci L Neurooncol Adv. 2023; 5(1):vdad120.

PMID: 37885806 PMC: 10599397. DOI: 10.1093/noajnl/vdad120.

LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization.

Hu R, Xu B, Ma J, Li L, Zhang L, Wang L Mol Med. 2023; 29(1):1.

PMID: 36604626 PMC: 9817280. DOI: 10.1186/s10020-022-00598-y.

E2F transcription factor 1/small nucleolar RNA host gene 18/microRNA-338-5p/forkhead box D1: an important regulatory axis in glioma progression.

Ma Q, Yang T Bioengineered. 2021; 13(1):418-430.

PMID: 34937497 PMC: 8805867. DOI: 10.1080/21655979.2021.2005990.

References

Cao S, Wang Y, Li J, Lv M, Niu H, Tian Y . Tumor-suppressive function of long noncoding RNA MALAT1 in glioma cells by suppressing miR-155 expression and activating FBXW7 function. Am J Cancer Res. 2016; 6(11):2561-2574. PMC: 5126273. View

Zheng Y, Hu W, Chen B, Grahn T, Zhao Y, Bao H . BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin. Liver Int. 2016; 36(12):1836-1847. DOI: 10.1111/liv.13178. View

Zhou W, Feng X, Ren C, Jiang X, Liu W, Huang W . Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma. Mol Cancer. 2013; 12:53. PMC: 3698204. DOI: 10.1186/1476-4598-12-53. View

Wang J, Li C, Xu L, Yang C, Zhang X . MiR-1193 was sponged by LINC00963 and inhibited cutaneous squamous cell carcinoma progression by targeting SOX4. Pathol Res Pract. 2019; 215(10):152600. DOI: 10.1016/j.prp.2019.152600. View

Yang F, Zhang J, Jin J, Yang C, Zhang W, Zhang H . HOXA11-AS promotes the growth and invasion of renal cancer by sponging miR-146b-5p to upregulate MMP16 expression. J Cell Physiol. 2018; 233(12):9611-9619. DOI: 10.1002/jcp.26864. View

Yong W, Yu D, Jun Z, Yachen D, Weiwei W, Midie X . Long noncoding RNA NEAT1, regulated by LIN28B, promotes cell proliferation and migration through sponging miR-506 in high-grade serous ovarian cancer. Cell Death Dis. 2018; 9(9):861. PMC: 6113267. DOI: 10.1038/s41419-018-0908-z. View

Song Z, Wang H, Zong F, Zhu C, Tao Y . MicroRNA‑506 regulates apoptosis in retinoblastoma cells by targeting sirtuin 1. Cancer Manag Res. 2019; 11:8419-8429. PMC: 6754339. DOI: 10.2147/CMAR.S211122. View

Tan H, Wang C, Liu G, Zhou X . Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3. J Cell Biochem. 2018; 120(4):4827-4836. DOI: 10.1002/jcb.26691. View

Beyer S, Fleming J, Meng W, Singh R, Haque S, Chakravarti A . The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas. Cancers (Basel). 2017; 9(7). PMC: 5532621. DOI: 10.3390/cancers9070085. View

10.

Lu Y, Cai X, Li Z, Lv J, Xiang Y, Chen J . LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma. Cell Physiol Biochem. 2018; 45(5):1975-1985. DOI: 10.1159/000487974. View

11.

Zheng J, Liu X, Wang P, Xue Y, Ma J, Qu C . CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis. Mol Ther. 2016; 24(7):1199-1215. PMC: 5088760. DOI: 10.1038/mt.2016.71. View

12.

Peng T, Zhou L, Zuo L, Luan Y . MiR-506 functions as a tumor suppressor in glioma by targeting STAT3. Oncol Rep. 2015; 35(2):1057-64. DOI: 10.3892/or.2015.4406. View

13.

Zhang N, Zeng X, Sun C, Guo H, Wang T, Wei L . LncRNA LINC00963 Promotes Tumorigenesis and Radioresistance in Breast Cancer by Sponging miR-324-3p and Inducing ACK1 Expression. Mol Ther Nucleic Acids. 2019; 18:871-881. PMC: 6881674. DOI: 10.1016/j.omtn.2019.09.033. View

14.

Wu J, Tian X, An Q, Guan X, Hao C . LINC00963 promotes hepatocellular carcinoma progression by activating PI3K/AKT pathway. Eur Rev Med Pharmacol Sci. 2018; 22(6):1645-1652. DOI: 10.26355/eurrev_201803_14574. View

15.

Rynkeviciene R, Simiene J, Strainiene E, Stankevicius V, Usinskiene J, Kaubriene E . Non-Coding RNAs in Glioma. Cancers (Basel). 2018; 11(1). PMC: 6356972. DOI: 10.3390/cancers11010017. View

16.

Wang L, Han S, Jin G, Zhou X, Li M, Ying X . Linc00963: a novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence. Int J Oncol. 2014; 44(6):2041-9. DOI: 10.3892/ijo.2014.2363. View

17.

Zhou Y, Yin L, Li H, Liu L, Xiao T . The LncRNA LINC00963 facilitates osteosarcoma proliferation and invasion by suppressing miR-204-3p/FN1 axis. Cancer Biol Ther. 2019; 20(8):1141-1148. PMC: 6605988. DOI: 10.1080/15384047.2019.1598766. View

18.

Zhou Q, Liu J, Quan J, Liu W, Tan H, Li W . MicroRNAs as potential biomarkers for the diagnosis of glioma: A systematic review and meta-analysis. Cancer Sci. 2018; 109(9):2651-2659. PMC: 6125451. DOI: 10.1111/cas.13714. View

19.

Lyu K, Xu Y, Yue H, Li Y, Zhao J, Chen L . Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21. Cancer Manag Res. 2019; 11:8487-8498. PMC: 6756574. DOI: 10.2147/CMAR.S213690. View

20.

Lei R, Xue M, Zhang L, Lin Z . Long noncoding RNA MALAT1-regulated microRNA 506 modulates ovarian cancer growth by targeting iASPP. Onco Targets Ther. 2016; 10:35-46. PMC: 5182047. DOI: 10.2147/OTT.S112686. View