KIAA1429 Induces m6A Modification of LINC01106 to Enhance the Malignancy of Lung Adenocarcinoma Cells via the JAK/STAT3 Pathway

Abstract

Background: Sustained expression of the long noncoding RNA (lncRNA) LINC01106 in tumors is crucial for the malignant phenotype of tumor cells. Nevertheless, the mechanisms and clinical effects of LINC01106 in lung adenocarcinoma (LUAD) are limited. This study shows the effect of vir-like m6A methyltransferase-associated (KIAA1429)-mediated N6-methyladenosine (m6A) modification on steady LINC01106 expression on LUAD progression.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine LINC01106 and KIAA1429 levels in LUAD tissues. Transwell, 5-ethynyl-2'-deoxyuridine (EdU), and cell counting kit-8 (CCK-8) assays were used to analyze the functional roles of LINC01106. A xenograft was constructed to verify the function of silencing LINC01106 in tumor growth. The regulatory role of LINC01106 was investigated using methylated RNA immunoprecipitation (MeRIP), qRT-PCR, and the actinomycin D assay. Western blotting was used to identify key proteins in the JAK/STAT3 (JAK2, STAT3) pathway.

Results: LINC01106 and KIAA1429 were highly expressed in LUAD, and LINC01106 was interconnected with high tumor grade, stage, and poor prognosis. Data revealed that LINC01106 inhibition reduced LUAD cell proliferation, invasion, and migration and restrained LUAD cell tumorigenicity. In addition, LINC01106 silencing reduced phosphorylated JAK2 and STAT3 levels. KIAA1429-mediated LINC01106 enhances its m6A modification and expression in LUAD cells. Moreover, KIAA1429 promotion eliminated the malignant phenotypic suppression induced by low expression in LUAD cells.

Conclusion: This study showed that KIAA1429 enhanced LINC01106 m6A modification to promote LUAD development. These results may lead to a better understanding of the mechanism of KIAA1429-m6A-LINC01106 in LUAD and offer a valuable therapeutic target for LUAD.