Tobacco carcinogen NNK promotes pancreatic cancer proliferation via LINC00857/β-catenin

Smoking is a key risk factor for pancreatic cancer (PC). Nicotine-derived nitrosamine ketone (NNK), a major tobacco smoke constituent, has been shown to promote cancer growth, but its specific role in PC progression remains unclear. While long non-coding RNA LINC00857 (lnc RNA) is implicated in cancer progression, its regulation by NNK is unknown. This study aims to investigate whether NNK can drive PC growth and elucidate the underlying mechanisms.

Employing an experimental methodology, this investigation treated human pancreatic cancer cell lines (CFPAC-1 and Panc-1) with NNK and utilized various assays (CCK-8, colony formation, and EdU cell proliferation) to assess the effects on cell proliferation. The interplay between LINC00857 expression profiles, PC, and smoking was systematically investigated through cross-database bioinformatic interrogation encompassing public resources and institutional biobank data. Experiments were performed to knock down LINC00857 in PC cells using siRNA technology. We used Western blotting and quantitative real-time PCR (qRT-PCR) to assess β-catenin expression and elucidate the mechanism by which the tobacco carcinogen NNK promotes PC formation.

Some evidence that NNK enhanced the proliferative capacity of PC cells was found. Bioinformatic analysis of public databases, combined with data from our center's database, revealed that LINC00857 was up-regulated in PC and correlated with smoking. Moreover, we discovered that knockdown of LINC00857 inhibited PC cell proliferation, with β-catenin identified as a potential downstream molecule. Importantly, after LINC00857 knockdown, we observed suppression of NNK-induced β-catenin upregulation at both protein and transcriptional levels.

NNK potentially induces PC progression through the LINC00857/β-catenin axis. These findings provide new perspectives on the mechanisms of PC progression and highlight the clinical relevance of smoking cessation for preventing PC.