UP scientists link vaping to tumor-forming changes in lung cells

By Francis Allan L. Angelo

QUEZON CITY – Molecular biologists from the University of the Philippines Diliman have produced new evidence that vaping triggers tumorigenic effects in human lung cells, adding to reports that e-cigarette smoke can significantly alter the transcriptome of respiratory epithelia.

Daniel Angelo Mirador, Jose Lorenzo Ferrer, Kim Denyse Hao Lin, and Dr. Reynaldo Garcia of the UP Diliman College of Science’s National Institute of Molecular Biology and Biotechnology examined how e-cigarette use may affect cancer-related cellular processes.

The team focused on a molecule it named vape-associated lncRNA transcript 1, or VALT1, which was found to be elevated in vape users and in certain lung cancer tumors.

The researchers then studied how VALT1 behaves in human cells exposed to e-cigarette vapor.

Garcia said the work grew out of an earlier study the group published in Scientific Reports on a different long noncoding RNA, the smoke- and cancer-associated lncRNA transcript 1, or SCAL1.

“In an earlier study that we published in Scientific Reports, we reported that the long noncoding RNA called smoke- and cancer-associated lncRNA transcript 1 (SCAL1) ensures the survival of cancer cells whose DNA has been damaged by cigarette smoke. It does so by detoxifying cells of reactive oxygen species (ROS) that would otherwise lead to cell death. This creates a paradox: instead of dying, the damaged cells persist, which can promote cancer development—creating a kind of double jeopardy,” Garcia explained.

“The motivation for this study was to ask whether a similar mechanism also occurs with vaping: can vape exposure trigger changes in cells that, like cigarette smoke, allow damaged cells to survive?” he added.

The team demonstrated that exposure to vape chemicals raises VALT1 levels and, at the same time, enhances cell proliferation, resistance to programmed cell death, cell migration, ROS detoxification, cytoskeletal disorganization, and nuclear remodeling, the same hallmarks observed in tumorigenic cells.

Overexpression of VALT1 can produce these effects even without vape exposure, the researchers found.

VALT1 can also promote the survival of cells under cytotoxic stress, such as the lung cancer cell line A549, but not its normal counterpart.

“This provides evidence that vaping is not safe, and that its harmful effects are mediated, at least partly, by VALT1. Our cells assume tumorigenic properties upon exposure to e-cigarettes,” Mirador said.

“Beyond its health implications, this work also contributes to our knowledge of non-coding RNA biology. The study of non-coding RNAs is relatively recent. They were initially dismissed as junk but are now established to have roles in both normal cell physiology and disease pathogenesis,” he added.

While e-cigarettes may carry a lower chemical load, they have been implicated in severe respiratory illnesses and cardiovascular damage.

The team cautioned that it may take decades to fully understand the long-term effects of e-cigarettes, including whether they contribute to cancer, because lung oncogenesis has a long induction and latency period while vaping has not been around for a long period of time.

Studies on the effects of vaping at the cellular and molecular level also remain limited, the researchers said, underscoring the need for further investigations to build a stronger scientific foundation.

The study, “Vape-Associated lncRNA Transcript 1 (VALT1) Amplifies the Tumorigenic Effects of e-Cigarette Vapor in Lung Epithelial Cells,” is published in Non-Coding RNA, an international, peer-reviewed, open-access journal on regulatory non-coding RNAs. (With a report from Eunice Jean C. Patron)