LncRNA DGUOK-AS1 facilitates non-small cell lung cancer growth and metastasis through increasing TRPM7 stability via m6A modification

Yimin Feng; Fengjuan Wu; Yuanning Wu; Zihan Guo; Xiang Ji

doi:10.1016/j.tranon.2023.101661

LncRNA DGUOK-AS1 facilitates non-small cell lung cancer growth and metastasis through increasing TRPM7 stability via m6A modification

Transl Oncol. 2023 Jun:32:101661. doi: 10.1016/j.tranon.2023.101661. Epub 2023 Apr 8.

Authors

Yimin Feng¹, Fengjuan Wu², Yuanning Wu³, Zihan Guo³, Xiang Ji⁴

Affiliations

¹ Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, China.
² Department of Pulmonary and Critical Care Medicine, Heze Municipal Hospital, Heze, Shandong 274031, China.
³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, No.16766 Jingshi Road, Jinan, Shandong 250014, China.
⁴ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, No.16766 Jingshi Road, Jinan, Shandong 250014, China. Electronic address: drjixiang@126.com.

Abstract

Background: N6-methyladenosine (m6A) modification plays key roles in tumor progression. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumors, but its role and mechanism in non-small cell lung cancer (NSCLC) development remain uncertain.

Methods: Cell proliferation, migration, invasion and angiogenesis were investigated via CCK-8, colony formation, transwell, and tube formation assays, respectively. The location of DGUOK-AS1 was detected via FISH assay. The interaction relationship among DGUOK-AS1, IGF2BP2 and TRPM7 was confirmed by RIP and MeRIP assays. The effects of DGUOK-AS1 on NSCLC growth and metastasis in vivo were investigated using xenograft and pulmonary metastatic models.

Results: DGUOK-AS1 was upregulated in NSCLC. DGUOK-AS1 silencing inhibited NSCLC cell proliferation, migration, invasion and angiogenesis. DGUOK-AS1 was mostly expressed in cytoplasm, and positively regulated IGF2BP2. METTL3/IGF2BP2 axis could increase TRPM7 mRNA stability in m6A-dependent manner. TRPM7 overexpression reversed the inhibitive function of DGUOK-AS1 silencing on NSCLC development. DGUOK-AS1 knockdown suppressed NSCLC cell growth and metastasis in nude mice.

Conclusion: DGUOK-AS1 silencing restrains NSCLC cell growth and metastasis through decreasing TRPM7 stability via regulation of the METTL3/IGF2BP2-mediated m6A modification.

Keywords: DGUOK-AS1; Growth; Metastasis; NSCLC; m6A modification.