Discovery of RNA molecule involved in oral cancer progression - Hopes for development of treatments at Sapporo Medical University

A research group led by Assistant Professor Takeshi Niinuma and Professor Hiromu Suzuki of the Department of Molecular Biology, School of Medicine, in collaboration with Associate Professor Tatsuya Sato of the Department of Cellular Physiology and Signal Transduction and Professor Akihiro Miyazaki of the Department of Oral Surgery at Sapporo Medical University, has announced that they discovered "LINC02154," an RNA molecule that promotes the proliferation of oral cancer cells, and clarified its mechanism of action. This molecule promotes the proliferation of cancer cells by regulating genes involved in the cell cycle and mitochondrial metabolism. They also found that regulation of target genes by LINC02154 involves its interaction with multiple microRNAs. The findings are expected to contribute to the development of a new therapeutic strategy for oral cancer. The results were published in the international journal Cancer Science on November 23.

Genes function via transcription from genomic DNA into messenger RNA followed by translation into proteins. Meanwhile, short noncoding RNAs (microRNAs), which are not translated into proteins, and long noncoding RNAs (lncRNAs), of which more than 10,000 different species are considered to exist, are also found in cells. Recent studies have revealed the molecular mechanisms of microRNAs and their relationships with diseases, but the function and significance of lncRNAs remain largely unknown, except that they are involved in differentiation and development of normal tissue and cancer progression.

In this study, the research group analyzed the expression of approximately 8,000 lncRNAs using a publicly available cancer genome database. They extracted lncRNAs that were upregulated in oral cancer and associated with a poor prognosis. They also investigated the effects of LINC02154 on cell growth and metabolism using an oral cancer cell line. Moreover, they searched for proteins and microRNAs that interact with LINC02154.

The results showed that LINC02154 was hardly expressed in normal tissues and overexpressed in oral cancer. LINC02154 was shown to promote cancer growth by regulating the expression of genes involved in the cell cycle and mitochondrial metabolism.

Suzuki said, "In this study, we have identified and reported a noncoding RNA molecule that appeared to contribute to the malignant transformation of oral cancer through two different mechanisms. The functions of most noncoding RNAs remain unknown, but we will continue our research, believing that elucidation of their functions will contribute to advancement in the treatment of patients with cancer."

Journal Information
Publication: Cancer Science
Title: LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma
DOI: 10.1111/cas.16379