Biology

Cisplatin and phenanthriplatin modulate long‑noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β‑catenin and TGF‑β signaling by
Jerry D. Monroe, Satya A. Moolani, Elvin N. Irihamye, Katheryn E. Lett, Michael D. Hebert, Yann Gibert, and Michael E. Smith in Scientific Reports (2021) 11:10408.

Different platinum chemotherapy compounds modulate distinct RNA targets to regulate important cancer cell signaling pathways

Cisplatin is a widely used platinum-based chemotherapy drug used to treat several cancers that unfortunately also causes side-effects by permanently damaging hearing, nervous system, and kidney tissue. A new platinum-based drug candidate, phenanthriplatin, has a different mechanism of action than cisplatin but can be even more effective against cancer cells. Prior research has suggested that compounds similar to phenanthriplatin may produce reduced toxicity in normal cells while still killing cancer cells, which might mean that they could act against cancer without causing side-effects.

New research published in Nature Research’s open access journal, Scientific Reports, found that cisplatin and phenanthriplatin may regulate distinct long-noncoding RNAs (lncRNAs) and microRNAs (miRNAs), which are different types of RNA that can interact with one another and regulate a variety of cellular mechanisms. Specifically, this work suggests that cisplatin and phenanthriplatin may act through different lncRNAs and miRNAs in both cancer and non-cancer cells to modulate two key pathways, Wnt/β-catenin and TGF-β, that regulate important cellular functions including cell growth, division, differentiation, and death. Thus, the data obtained from this project could assist the development of a new generation of platinum-based chemotherapy compounds which target specific pathways that cause cancer cell death while preventing damage to non-cancer cells and side-effects.

Researchers from Dr. Michael Smith’s laboratory in the Biology Department at Western Kentucky University and Dr. Yann Gibert’s laboratory in the Department of Cell and Molecular Biology at the University of Mississippi Medical Center collaborated on the project. Two high school students from the Gatton Academy of Mathematics and Science, Elvin Irihamye and Satya Moolani, isolated the RNA from the cell lines used in this project and were mentored by postdoctoral research associate, Dr. Dave Monroe, the lead author on the paper.

This research was supported by NIH R15 (T1 R15 CA188890-01A1) and IDeA Network of Biomedical Research Excellence grants (ULRF13-1493C-01) to Dr. Smith, and by a NIH (P20 GM104357) grant to Dr. Gibert.

For further information about this project, contact Dr. Michael Smith, michael.smith1@wku.edu.