LINC00426, a novel m6A-regulated long non-coding RNA, induces EMT in cervical cancer by binding to ZEB1

Siyuan Shen; Hua Jin; Xing Zhang; Yan Zhang; Xiuting Li; Wenjing Yan; Shuqian Xie; Bingjia Yu; Jing Hu; Haohan Liu; Xue Chen; Yamei Nie; Fengying Liu; Min Tang; Yun Gu; Shizhi Wang

doi:10.1016/j.cellsig.2023.110788

LINC00426, a novel m⁶A-regulated long non-coding RNA, induces EMT in cervical cancer by binding to ZEB1

Cell Signal. 2023 Sep:109:110788. doi: 10.1016/j.cellsig.2023.110788. Epub 2023 Jun 29.

Authors

Siyuan Shen¹, Hua Jin², Xing Zhang¹, Yan Zhang³, Xiuting Li⁴, Wenjing Yan¹, Shuqian Xie¹, Bingjia Yu¹, Jing Hu¹, Haohan Liu¹, Xue Chen¹, Yamei Nie¹, Fengying Liu¹, Min Tang², Yun Gu⁵, Shizhi Wang⁶

Affiliations

¹ Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
² Clinical Laboratory, Affiliated Tumor Hospital of Nantong University (Nantong Tumor Hospital), Nantong, China.
³ Shihezi University, School of Medicine, Department of Preventive Medicine, Shihezi, China.
⁴ School of Health Management and Basic Science, Jiangsu Health Vocational College, Nanjing, China.
⁵ Department of Pathology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. Electronic address: guyun1979@njmu.edu.cn.
⁶ Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China. Electronic address: shizhiwang2009@seu.edu.cn.

PMID: 37392859
DOI: 10.1016/j.cellsig.2023.110788

Abstract

Purpose: To explore the function and molecular mechanism of LINC00426 in Cervical Cancer (CC), and to explore the clinical treatment strategy of LINC00426 for CC.

Methods: Bioinformatics analysis was used to explore the expression of LINC00426 and patient prognosis of CC. Cell function experiments were conducted to explore the potential effect of LINC00426 on CC malignant phenotypes. The difference in m⁶A modification level between the high and low expression groups of LINC00426 was analyzed by detecting the total m⁶A level. The luciferase reporter assay was used to confirm the binding of miR-200a-3p to LINC00426. The RIP assay was used to confirm the binding of LINC00426 to ZEB1. Cell viability assay was performed to detect the effect of LINC00426 on cellular drug resistance.

Results: LINC00426 is up-regulated in CC, which can enhance the proliferation, migration and invasion of CC cells. METTL3 promotes the expression of LINC00426 by m⁶A methylation modification. In addition, the LINC00426/miR-200a-3p/ZEB1 axis affects the proliferation, migration, and invasion of CC by regulating the expression of EMT markers. Through the detection of cell viability, we observed that overexpression LINC00426 in cells resulted in resistance to cisplatin and bleomycin, and more sensitive to imatinib.

Conclusion: LINC00426 is a cancer-promoting lncRNA related to m⁶A modification. The process of EMT in CC is regulated by the LINC00426/miR-200a/3p/ZEB1 axis. LINC00426 can affect the sensitivity of CC cells to chemotherapy drugs, and is expected to become a therapeutic target for CC.

Keywords: Cervical cancer; Drug resistance; LINC00426; ZEB1; m(6)A; miR-200a-3p.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation / genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Methyltransferases / metabolism
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Uterine Cervical Neoplasms* / metabolism
Zinc Finger E-box-Binding Homeobox 1 / genetics
Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

MicroRNAs
RNA, Long Noncoding
ZEB1 protein, human
Zinc Finger E-box-Binding Homeobox 1
METTL3 protein, human
Methyltransferases