Regulation of cell proliferation and xenograft tumor growth by LncRNA67 in triple-negative breast cancer cells
Introduction
Breast cancer is the second leading cause of cancer mortality in women. It is categorized into different molecular subtypes, with triple-negative breast cancer (TNBC) accounting for about 10-15% of cases. TNBC is highly aggressive and challenging to treat due to the lack of specific therapeutic targets, leading to a worse prognosis than other types of breast cancer. Recent studies have highlighted the significance of non-coding transcripts in gene regulation and other biological processes, including cancer, as next-generation sequencing technologies advance. Genes involved in cancers that are transcribed using a process known as divergent transcription have been implicated in recent studies. The expression of these genes is tightly regulated, but many escape regulation and become aberrantly expressed in tumors.
Methods
Our genomic analysis suggests that several genes encode noncoding transcripts, such as long noncoding RNAs (lncRNAs). For example, lncRNA67 is transcribed divergently from the neighboring gene PDCD6IP is estrogen-regulated, and modulates cell cycle and cell proliferation in ER-positive breast cancer cell lines. We quantified the expression of lncRNA67 in normal and breast cancer tissues of various molecular subtypes using the RNAscope technique.
Results
We found that compared to normal tissue, lncRNA67 is up-regulated in both ER-positive and TNBC cancers, which led us to study its function and role in the TNBC context. Our findings indicate that lncRNA67 significantly reduces cell proliferation in MDA-MB-231 cells and tumor growth in a mouse xenograft model.
Conclusion
Collectively, our results suggest that divergent transcription could be an integral component of cancer biology and present a new repertoire of diagnostic and potential therapeutic targets.