HNRNPDL bevordert progressie van NSCLC via alternatieve splicing van het BTC-gen

INTRODUCTION: In the context of tumor diseases, aberrant splicing has become a potential source for targeted treatment. In this work, we discovered a 147-bp splicing anomaly in the downstream target gene BTC, which is regulated by the HNRNPDL gene in non-small cell lung cancer. The biological significance and therapeutic relevance of this splicing regulation remain unclear. METHODS: RNA sequencing (RNA-seq) was used to carefully screen for differential genes downstream of HNRNPDL that were transfected into NSCLC cell lines using lentivirus-mediated short hairpin RNA (shRNA). As a result, key splicing events linked to NSCLC were identified. Additionally, NSCLC cell lines received shRNA plasmids that targeted different spliceosomes of HNRNPDL and BTC, which sparked a series of in vitro tests intended to clarify their biological functions. RESULTS: There was an up-regulation of the HNRNPDL expression profile. Due to exon 4 aberrancy, the RNA-seq study concurrently produced two transcripts, namely exon 4 (BTC-L) and exon 4 skipping transcripts (BTC-S). In contrast to normal bronchial cells (BEAS-2B), BTC-L and BTC-S were both significantly up-regulated in NSCLC cell lines. Experiments conducted in vitro clearly demonstrated that both BTC-L and BTC-S could promote the migration and proliferation of non-small cell lung cancer cells and inhibit their apoptosis, showing comparable oncogenic phenotypes in vitro. CONCLUSIONS: Our findings suggest that HNRNPDL may contribute to NSCLC progression by regulating BTC alternative splicing.