PPP1R14B Promotes Lung Adenocarcinoma Tumorigenesis and Paclitaxel Resistance by Increasing ARPC1A Expression

To investigate the biological functions of PPP1R14B in lung adenocarcinoma and further elucidate its underlying regulatory mechanisms. The Cancer Genome Atlas clinical cohorts, single-cell sequencing, Kaplan-Meier survival analysis, immunohistochemistry, qRT-PCR, and Western blot were performed to assess the expression and prognostic value of PPP1R14B in lung adenocarcinoma. Then, PPP1R14B-silenced A549 cells and PPP1R14B-overexpressing H1650 cells were constructed. Colony formation, CCK-8, EdU assay, flow cytometry, scratch, and Transwell chamber assays were utilized to evaluate cell proliferation, apoptosis, migration, invasion, and paclitaxel (PTX) resistance. To elucidate the molecular mechanism of PPP1R14B, transcriptome sequencing (RNA-seq) and co-immunoprecipitation assays were conducted. Additionally, a xenograft tumor mouse model was established to explore the in vivo role of PPP1R14B. PPP1R14B exhibited high expression in lung adenocarcinoma and correlated with an unfavorable prognosis. Silencing of PPP1R14B markedly suppressed the proliferation, migration, and invasion of A549 cells, while concurrently promoting apoptosis and sensitizing cells to PTX. Nevertheless, overexpression of PPP1R14B in H1650 cells displayed an opposite trend. PPP1R14B directly interacted with ARPC1A and promoted its expression. Overexpression of ARPC1A reversed the inhibitory effects of PPP1R14B silencing on the malignant biological behaviors of A549 cells. In vivo, silencing of PPP1R14B repressed tumor growth, as evidenced by smaller tumor volume, lower tumor weight, fewer Ki67-positive cells, and more TUNEL-positive cells. PPP1R14B directly binds ARPC1A and increases its expression to facilitate lung adenocarcinoma tumorigenesis and PTX resistance.