Upregulation of M6A Reader HNRNPA2B1 Associated with Poor Prognosis and Tumor Progression in Lung Adenocarcinoma.

Abstract

Background: Lung cancer is the most prevalent malignancy worldwide, and lung adenocarcinoma (LUAD) accounts for a substantial proportion of all cases. N6-methyladenosine (m6A) is the most frequent post-transcriptional modification in mRNAs that also plays a role in cancer development. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is a reader of m6A modification, which can affect tumor invasion, migration, and proliferation.

Objectives: The purpose of this study was to explore the prognostic factors of LUAD based on m6A through bioinformatics analysis.

Materials and methods: The expression levels and prognostic significance of HNRNPA2B1 in LUAD were analyzed on the basis of data extracted from the UALCAN, GEPIA, NCBI-GEO, Human Protein Atlas, STRING, miRDB, TargetScan, PROMO, Starbase, UCSC Xena browser, TIMER, and TISIDB databases. HNRNPA2B1 protein and mRNA levels in several LUAD cell lines were detected by western blotting and qRT-PCR. CCK8, wound-healing and transwell assays were performed to evaluate the proliferation, invasion, and migration abilities of LUAD cells.

Results: HNRNPA2B1 mRNA was found to be significantly overexpressed in LUAD tissues, and its high levels correlated with poor OS and DFS. The genes co-expressed with HNRNPA2B1 were related to mRNA production, cell cycle, and histone binding. To determine the mechanistic basis of HNRNPA2B1 in LUAD, we next predicted the microRNAs and transcription factors that were directly associated with HNRNPA2B1, as well as copy number changes. In addition, it was found that HNRNPA2B1 expression was significantly related to CD⁴⁺ T cells, neutrophils, lymphocytes, immunomodulators, and chemokines. Besides, knocking down HNRNPA2B1 in the LUAD cells led to a significant reduction in their proliferation, invasion, and migration rates in vitro.

Conclusion: Elevated HNRNPA2B1 is a risk factor in LUAD and portends a poor prognosis.