High level of LncRNA MAPKAPK5-AS1 predicts poor prognosis and contributes to the malignant proliferation and EMT of non-small cell lung cancer via sponging miR-490-3p from HMGB2.

Abstract

BACKGROUND:

Patients with non-small cell lung cancer (NSCLC) show a low survival rate, owing to the lack of early diagnostic method and high invasiveness. Long non-coding RNA MAPKAPK5-AS1 that regulates tumor genesis and progression through multiple signals, is upregulated and involved in the growth and apoptosis in lung adenocarcinoma (LUAD).

OBJECTIVE:

To investigate whether MAPKAPK5-AS1 affected the malignant progression of NSCLC.

METHODS:

The levels of MAPKAPK5-AS1, miR-490-3p and HMGB2 in lung cancer were first analyzed through StarBase website, and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay. The biological functions of NSCLC cells were examined by CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays. The potential binding sequences lncRNA-miRNA and miRNA-mRNA were predicted by StarBase software and verified via dual luciferase reporter experiment. The effects of MAPKAPK5-AS1 on tumor growth were evaluated in a xenografted mice model.

RESULTS:

The expression of MAPKAPK5-AS1 was upregulated in tumor tissues from NSCLC patients. Patients with high expression of MAPKAPK5-AS1 had higher tumor size, advanced TNM stage, higher incidence of lymph node and distant metastasis, and shorter overall survival. Knockdown of MAPKAPK5-AS1 inhibited the proliferation, induced apoptosis and blocked epithelial mesenchymal transformation (EMT) of NSCLC cells. Mechanically, MAPKAPK5-AS1 could upregulate the HMGB2 level in NSCLC cells through competitively binding to miR-490-3p. MiR-490-3p inhibitor reversed the roles of MAPKAPK5-AS1 knockdown on tumor cell proliferation, apoptosis and EMT. Also, HMGB2 knockdown suppressed tumor cell malignant phenotypes. Furthermore, interference of MAPKAPK5-AS1 slowed NSCLC tumor growth in vivo.

CONCLUSION:

Knockdown of MAPKAPK5-AS1 inhibited the aggressive tumor phenotypes through miR-490-3p/HMGB2 axis in NSCLC. MAPKAPK5-AS1/miR-490-3p/HMGB2 might be potential biomarkers or therapeutic targets for NSCLC.

• Authors: Jidong Miao, Yang Gao, Wenqiang Guan, Xiaolin Yu, Yong Wang, Ping Jiang, Lili Yang, Lun Xu, Wei You
• Journal: Genes & genomics (Genes Genomics) Vol. 45 Issue 5 Pg. 611-625 (05 2023) ISSN: 2092-9293 [Electronic] Korea (South)
• PMID: 36445573 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.

Chemical References

• RNA, Long Noncoding
• HMGB2 Protein
• MAP-kinase-activated kinase 5
• MicroRNAs
• Transcription Factors

Topics

• Animals
• Mice
• Carcinoma, Non-Small-Cell Lung (pathology)
• Lung Neoplasms (metabolism)
• RNA, Long Noncoding (genetics)
• HMGB2 Protein (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• MicroRNAs (genetics, metabolism)
• Cell Proliferation (genetics)
• Transcription Factors
• Disease Models, Animal
• Prognosis