m6A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis

Xingwei Wu; Minjie Fu; Chang Ge; Hanyu Zhou; Haoyu Huang; Min Zhong; Mengying Zhang; Hao Xu; Guoping Zhu; Wei Hua; Kun Lv; Hui Yang

doi:10.1007/s12035-023-03911-w

m⁶A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis

Mol Neurobiol. 2024 Jan 9. doi: 10.1007/s12035-023-03911-w. Online ahead of print.

Authors

Xingwei Wu^#^{1

2

3}, Minjie Fu^#^{4

5}, Chang Ge^#⁶, Hanyu Zhou^{1

2

3

6}, Haoyu Huang^{1

2

3}, Min Zhong^{1

2

3

6}, Mengying Zhang^{1

2

3

6}, Hao Xu⁴, Guoping Zhu^{7

8

9}, Wei Hua^{10

11}, Kun Lv^{12

13

14

15

16

17

18}, Hui Yang^{19

20

21

22

23

24

25}

Affiliations

¹ Anhui Province Key Laboratory of Non-Coding RNA Basic Research and Clinical Transformation, Wannan Medical College, Wuhu, 241001, China.
² Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, China.
³ Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.
⁴ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
⁵ Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Neurosurgical Institute of Fudan University, Shanghai, China.
⁶ Department of Psychology, Zhejiang Sci-Tech University, Hangzhou, 310000, Zhejiang, China.
⁷ Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, College of Life Sciences, Anhui Normal University, Wuhu, 241001, Anhui, China. gpz2012@ahnu.edu.cn.
⁸ College of Life Sciences, Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, Anhui Normal University, Wuhu, 241001, Anhui, China. gpz2012@ahnu.edu.cn.
⁹ Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu, 241001, Anhui, China. gpz2012@ahnu.edu.cn.
¹⁰ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China. hs_huawei@126.com.
¹¹ Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Neurosurgical Institute of Fudan University, Shanghai, China. hs_huawei@126.com.
¹² Anhui Province Key Laboratory of Non-Coding RNA Basic Research and Clinical Transformation, Wannan Medical College, Wuhu, 241001, China. lvkun315@126.com.
¹³ Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, China. lvkun315@126.com.
¹⁴ Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China. lvkun315@126.com.
¹⁵ Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, College of Life Sciences, Anhui Normal University, Wuhu, 241001, Anhui, China. lvkun315@126.com.
¹⁶ College of Life Sciences, Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, Anhui Normal University, Wuhu, 241001, Anhui, China. lvkun315@126.com.
¹⁷ Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu, 241001, Anhui, China. lvkun315@126.com.
¹⁸ Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China. lvkun315@126.com.
¹⁹ Anhui Province Key Laboratory of Non-Coding RNA Basic Research and Clinical Transformation, Wannan Medical College, Wuhu, 241001, China. yanghui0203@wnmc.edu.cn.
²⁰ Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, China. yanghui0203@wnmc.edu.cn.
²¹ Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China. yanghui0203@wnmc.edu.cn.
²² Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, College of Life Sciences, Anhui Normal University, Wuhu, 241001, Anhui, China. yanghui0203@wnmc.edu.cn.
²³ College of Life Sciences, Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, Anhui Normal University, Wuhu, 241001, Anhui, China. yanghui0203@wnmc.edu.cn.
²⁴ Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu, 241001, Anhui, China. yanghui0203@wnmc.edu.cn.
²⁵ Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China. yanghui0203@wnmc.edu.cn.

^# Contributed equally.

PMID: 38193984
DOI: 10.1007/s12035-023-03911-w

Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/β-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N⁶-methyladenosine(m⁶A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/β-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.

Keywords: Glioma; N 6-methyladenosine; TRIM14; lncRNA CHASERR; miR-6893-3p.

Abstract

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