miR-197-5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101.

The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR-197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR-197-5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90-tert fibroblast cells. The transient overexpression of miR-197-5p causes a significant decrease in viability and proliferation of fibrosarcoma cells in both concentration- and time-dependent manners. Interestingly, we did not observe any significant changes in cell cycle pattern or apoptotic cell populations, but rather noticed cellular senescence of fibrosarcoma cells upon overexpression of miR-197-5p. Further, this miRNA suppresses the metastatic properties, such as migration, invasion, and anchorage-independent growth of fibrosarcoma possibly through targeting KIAA0101, which is a proliferating cell nuclear antigen-associated factor and overexpressed in the malignancy. In nutshell, our result revealed that miR-197-5p acts as an oncosuppressor miRNA in fibrosarcoma through target regulation of KIAA0101, which can be exploited for developing RNA-based therapeutic strategies for the cure of this malignancy.