Epigenetic Study Reveals How RNA Methylation Changes Drive Lung Cancer Progression

A study in the Journal of Advanced Research has uncovered how cigarette smoke–derived carcinogens fuel lung cancer by hijacking RNA methylation. The findings reveal that the RNA demethylase ALKBH5 promotes tumor growth by stabilizing the COL5A1 gene message, ultimately advancing the development and spread of tobacco-induced lung cancer.

Linking RNA Methylation to Lung Cancer

Lung cancer remains one of the leading causes of cancer mortality worldwide, with tobacco smoke being the single largest risk factor. While genetic mutations are well known to drive tumorigenesis, epitranscriptomic changes—chemical modifications on RNA that regulate its fate without altering the genetic code—are now recognized as powerful drivers of cancer biology.

Among these, N6-methyladenosine (m6A) is the most abundant RNA modification, shaping RNA stability, translation, and localization. The balance of m6A “writers,” “erasers,” and “readers” ensures normal cell behavior, but disruption of this system can give cancer cells a major growth advantage.

Inside the Study

Researchers investigated how exposure to NNK, a potent carcinogen derived from tobacco, alters RNA regulation in lung cells. They discovered that NNK strongly activates ALKBH5, an m6A “eraser” enzyme. By stripping away m6A marks on COL5A1 mRNA, ALKBH5 prevents its normal degradation, causing COL5A1 to accumulate. Elevated COL5A1 levels promote uncontrolled cell growth, invasion, and progression of lung cancer.

To precisely track these RNA methylation changes, the team used EpigenTek’s EpiQuik™ m6A RNA Methylation Quantification Kit, a colorimetric platform for accurate detection of m6A levels in RNA samples. The kit confirmed that COL5A1 transcripts lost their m6A marks when ALKBH5 was activated, directly linking NNK exposure to a cancer-promoting RNA demethylation pathway.

Epitranscriptomic Insights Into Tobacco Carcinogenesis

These findings show how tobacco smoke exploits RNA methylation pathways to fuel cancer. By boosting ALKBH5 activity, carcinogens like NNK can selectively protect tumor-promoting RNAs from degradation, creating an environment where cancer cells thrive. Targeting the ALKBH5–COL5A1 axis may open new therapeutic opportunities for patients with smoking-related lung cancer.

For researchers studying RNA methylation, EpigenTek provides fast, reliable solutions to profile m6A and related modifications. By offering complete assay systems, trusted antibodies, and robust controls, EpigenTek empowers scientists to uncover the hidden RNA mechanisms driving cancer and other diseases.

Enhance Your RNA Study

Whether you’re investigating RNA methylation or other aspects of epitranscriptomics, EpigenTek delivers the tools and support you need to accelerate discoveries. Backed by our performance guarantee and expert technical assistance, our kits help ensure reproducible, high-impact results. Contact us today to learn how we can support your research.