RNA affecting skin cancer progression spotted

Researchers at the University of Turku, the Turku University Central Hospital, and the Western Cancer Centre (FICAN West) have discovered a new RNA molecule, PRECSIT, which regulates the growth and invasion of squamous cell carcinoma of the skin.

In the future, PRECSIT could potentially serve as a new marker for detection of rapidly advancing or spreading of the squamous cell carcinoma and as a target for new therapies, said the University of Turku in a press release.

Skin cancers are the most common in the world and their incidence is increasing. Squamous cell carcinoma is the most common metastatic skin cancer and its incidence is increasing worldwide.

Long-term exposure to the sun’s ultraviolet radiation is the most important risk factor for development of this type of cancer.

“Squamous cell carcinoma of the skin is characterised by a significant gene mutation burden of cancer cells resulting from long-term exposure to the sun’s ultraviolet radiation. Several gene mutations predisposing to skin cancer are known, but the importance of non-coding RNA molecules of the so-called dark side of the genome in the development of squamous cell carcinoma is still unclear,” said Professor Veli-Matti Kähäri from the Department of Dermatology of the University of Turku.

“The majority of the human genome contains genes that do not produce protein, but their role as regulators of cellular functions is still essential. Long non-coding RNAs are a largely unknown set of RNAs and recent studies have found that they play a role in regulating signalling pathways, particularly in cancer,” said Minna Piipponen, one of the researchers and one of the authors of the study report.

Thus, she said, RNA molecules could be utilised in cancer diagnostics as specific marker molecules and as targets for new therapies.

PRECSIT regulates the growth and spread of squamous cell carcinoma

The study found that expression of a new long non-coding RNA in cancer cells of squamous cell carcinoma was elevated compared to healthy skin.

The study also showed that expression of PRECSIT is regulated by the tumour suppressor gene p53, which is inactivated by mutations in most squamous cell carcinomas. The researchers also discovered that PRECSIT promotes invasion of cancer cells by increasing the production of extracellular matrix cleaving proteolytic enzymes via the STAT3 signalling pathway.

Based on its expression and mechanism of action, this long non-coding RNA was named PRECSIT (p53-regulated carcinoma-associated STAT3-activating long intergenic non-protein-coding transcript).