Interaction between IGF2BP3 and RP11-480I12.5 facilitates proliferation and suppresses apoptosis in non-small cell lung cancer

Background: Non-small cell lung Cancer (NSCLC) is a malignant tumor type with the fastest growing incidence and mortality rates worldwide, accounting for over 80% of all lung Cancer cases and presenting a substantial menace to human health. Abnormal expression of long non-coding RNAs has been linked to the advancement of NSCLC. RP11-480I12.5 is highly overexpressed in NSCLC, nevertheless its function remains unknown.

Methods: qPCR was utilized to analyze the expression levels of RP11-480I12.5 in NSCLC cell lines. To elucidate the functional significance of RP11-480I12.5, H1650 and Calu-1 cells were infected with lentivirus carrying RP11-480I12.5-shRNA or IGF2BP3-shRNA. Subsequently, cell viability was assessed using the CCK-8 assay, cell proliferation capacity was evaluated through colony formation experiments, and Apoptosis rates were determined using flow cytometry. The interactions between RP11-480I12.5 and IGF2BP3 were assessed through RNA‑binding protein immunoprecipitation assay (RIP) and RNA pull-down assays.

Results: RP11-480I12.5 was considerably increased in both the lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) subtypes of NSCLC. IGF2BP3, which is extensively expressed in NSCLC, has poor predictive relevance, notably in LUAD. Interaction tests indicated a strong binding between RP11-480I12.5 and IGF2BP3, indicating a functional synergy in NSCLC pathogenesis. The co-regulated gene, WDHD1, which was considerably increased in NSCLC, facilitated the tumorigenic effects of the RP11-480I12.5-IGF2BP3 axis via influencing cell proliferation and death.

Conclusions: RP11-480I12.5 interacted with IGF2BP3 to increase WDHD1 expression, promoting NSCLC cell proliferation and anti-apoptotic ability. Current findings elucidate how RP11-480I12.5 and IGF2BP3 interact at the molecular level, which has important implications for the progression of NSCLC.

Apoptosis; IGF2BP3; NSCLC; Proliferation; RP11-480I12.5; WDHD1.