Moffitt Researchers Identify Tumor Suppressors in Cutaneous Squamous Cell Carcinoma
Posted: Friday, April 24, 2020
The protein TAp63, a member of the p53 family and potent tumor suppressor, was identified as a regulator of microRNAs, with the potential to be targeted for therapy in cutaneous squamous cell carcinoma. Elsa R. Flores, PhD, of the Moffitt Cancer Center and Research Institute in Tampa, Florida, and colleagues published this work in Cancer Research.
“Given the lack of FDA-approved targeted therapies for advanced cutaneous squamous cell carcinoma, our study provides preclinical evidence for the use of miR-30c-2*/miR-497 delivery or AURKA inhibition for the effective treatment approach,” said Dr. Flores in a Moffitt press release.
The team utilized mouse models to study animals both with and without mutated TAp63 who were exposed to ultraviolet light radiation. The tumors that developed in these mice were compared with tumors in xenograft models of cutaneous squamous cell carcinoma using RNA isolation, sequencing, and analysis.
Mice with mutant TAp63 developed a significantly higher number of cutaneous squamous cell tumors than mice with intact TAp63. In squamous cell tumors deficient in TAp63, the microRNAs miR-30c-2* and miR-497 were underexpressed. Upon reintroduction of these deficient microRNAs, growth of tumors and cell lines with TAp63 deletion were significantly inhibited. Researchers found that miR-30c-2* seemed to contribute to cell death, whereas miR-497 appeared to inhibit cell growth and proliferation.
Using a cross-platform comparison of RNA-sequencing and proteomics data, researchers identified a seven-gene signature that were overexpressed in cutaneous squamous cell carcinoma, including AURKA, KIF18B, PKMYT1, and ORC1. Knockdown of these genes suppressed tumor cell proliferation and was able to induce apoptosis. In addition, selective inhibition of AURKA was found to suppress cutaneous squamous cell carcinoma cell proliferation, induce apoptosis, and yield antitumor effects in vivo.
Disclosure: The study authors reported no conflicts of interest.
