KIAA1429 promotes the progression of lung adenocarcinoma by regulating the m6A level of MUC3A

Abstract

Objective: Lung adenocarcinoma (LUAD) is one of the most frequently occurring human malignancies worldwide, but its potential molecular mechanism has not yet been fully elucidated. N6-methyladenosine (m6A), the most common internal chemical modification of mRNAs, is implicated in diverse pathological processes in different human malignancies, but its functions in LUAD remain elusive. The current study aimed to investigate the function and molecular mechanism of KIAA1429 in LUAD.

Methods: The KIAA1429 expression level in LUAD tissues was assessed using databases and was detected in LUAD cells and tissues via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. m6A levels in LUAD tissues and cells were quantified. Next, correlation between the KIAA1429 expression level and the clinical and pathological features and prognosis of patients with LUAD was analyzed. Further, KIAA1429 levels were decreased, and LUAD cell proliferation, migration, invasion, and cycle were assessed. Prediction websites revealed the aberrant expression and probable methylation modification of MUC3A in LUAD, and correlation between MUC3A and KIAA1429 was analyzed. Ultimately, the impact of the KIAA1429 expression on MUC3A-mediated malignant phenotypes of LUAD was examined by a torsion test.

Results: KIAA1429 expression was remarkably high and m6A level was aberrantly elevated in LUAD cells and tissues. In addition, high KIAA1429 expression indicated a larger tumor diameter, higher tumor-node-metastasis stage, greater proneness to lymph node and distant metastasis, and lower overall survival rate. siRNA-triggered KIAA1429 downregulation dramatically suppressed LUAD cell proliferation, migration, invasion, and cell cycle arrest in the G1 phase. Bioinformatics analysis revealed that MUC3A was expressed in LUAD at an unusually high level and may be methylated under the control of KIAA1429. Western blot, qRT-PCR, and correlation analyses revealed a positive correlation between KIAA1429 expression level and MUC3A. Finally, torsion test results revealed that low KIAA1429 expression reversed LUAD cell migration, proliferation, and invasion facilitated by low MUC3A expression as well as cell cycle arrest in the G1 phase.

Conclusion: KIAA1429 exhibited an unusually high expression in LUAD cells and tissues, and high KIAA1429 expression was correlated with the clinical and pathological features of patients with LUAD, thereby leading to an unsatisfactory prognosis. Furthermore, KIAA1429 regulates MUC3A expression through m6A modification to modulate LUAD cells to proliferate, migrate, invade, and induce cell cycle arrest.

Keywords: Cell proliferation; KIAA1429; Lung adenocarcinoma; MUC3A; Methylation.