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

Abstract

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 anchorageindependent 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.

Restoration of microRNA‐197 expression suppresses oncogenicity in fibrosarcoma through negative regulation of RAN

“…miR‐29 family is reported to inhibit invasiveness of fibrosarcoma by targeting MMP2 . In addition, our lab has also identified two potential miRNAs, miR‐429 and miR‐197‐5p, in fibrosarcoma acting as tumor suppressor by targeting oncogenic protein, KIAA0101 …”

“…1,5 Recently, several miRNAs have been implicated in the tumorigenesis and progression of STS. 1 However, in fibrosarcoma, a very rare subtype of STS, only a few miRNAs, for example, miR-520c and miR-373, 28 miR-409-3p, 29 miR-429, 15 and miR-197-5p 16 have been studied so far.…”

“…Among numerous miRNAs studied so far, miR‐197 was found to be dysregulated in myriad of cancers such as non‐small cell lung cancer, hepatocellular carcinoma, gastric cancer, and colorectal cancer that plays a very critical role in cell proliferation, apoptosis, angiogenesis, metastasis, and drug resistance . miR‐197 corresponds to two mature miRNAs, miR‐197‐5p and miR‐197‐3p, out of which we have deciphered the role of the former in fibrosarcoma . Therefore, in this study, we intended to investigate the possible role of miR‐197‐3p in the sarcomagenesis and whether its function is similar to that of miR‐197‐5p, both of which are originated from different arms of the same precursor miRNA‐197.…”

“…14 In addition, our lab has also identified two potential miRNAs, miR-429 and miR-197-5p, in fibrosarcoma acting as tumor suppressor by targeting oncogenic protein, KIAA0101. 15,16 Among numerous miRNAs studied so far, miR-197 was found to be dysregulated in myriad of cancers such as non-small cell lung cancer, 17 hepatocellular carcinoma, 18 gastric cancer, 19 and colorectal cancer 20 that plays a very critical role in cell proliferation, apoptosis, angiogenesis, metastasis, and drug resistance. 21 miR-197 corresponds to two mature miRNAs, miR-197-5p and miR-197-3p, out of which we have deciphered the role of the former in fibrosarcoma.…”

“…21 miR-197 corresponds to two mature miRNAs, miR-197-5p and miR-197-3p, out of which we have deciphered the role of the former in fibrosarcoma. 16 Therefore, in this study, we intended to investigate the possible role of miR-197-3p in the sarcomagenesis and whether its function is similar to that of miR-197-5p, both of which are originated from different arms of the same precursor miRNA-197.…”