KIAA1429 facilitates progression of hepatocellular carcinoma by modulating m6A levels in HPN

Heliyon. 2023 Nov 8;9(11):e22084. doi: 10.1016/j.heliyon.2023.e22084. eCollection 2023 Nov.

Abstract

Background: Most N6-methyladenosine (m6A)-associated modulatory proteins are involved in the pathogenesis of various cancers. The roles of m6A-related genes in liver hepatocellular carcinoma (LIHC) and the associated mechanisms remain unknown.

Methods: GEO and GEPIA2 databases were used to identify the m6A modification-related genes which were differentially expressed in LIHC and adjacent non-tumor tissues, and quantitative PCR was used to evaluate the expression of KIAA1429, a major m6A methyltransferase, in LIHC cells. The effect of KIAA1429 on the malignant phenotypes of LIHC cells was evaluated in vitro. The UALCAN, GEPIA, and GEO databases and western blotting assays were used to identify the target genes of KIAA1429.

Results: KIAA1429 expression was markedly elevated in LIHC tissues, and patients with LIHC who had high KIAA1429 expression had a worse prognosis than those who had low expression. KIAA1429 silencing attenuated LIHC metastasis and proliferation. KIAA142 regulates m6A levels in HPN to intensify LIHC progression.

Conclusion: Our study suggests a KIAA1429-HPN modulatory model based on m6A modifications, that offers insights into the occurrence and development of LIHC.

Keywords: HPN; Hepatocellular carcinoma; KIAA1429; Migration; m6A methylation.