MicroRNA‐125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells

Abstract

Renal cell carcinoma (RCC) is one of the most common cancers in urology. MicroRNA-125a (miR-125a) has been demonstrated to be implicated in various cancers. However, the functional role of miR-125a in RCC remains largely unclear. This study was aimed to investigate the functional role of miR-125a and the expression relevance of signal transducers and activators of transcription 3 (STAT3) with hyaluronic acid synthase 1 (HAS1) in RCC. We revealed that miR-125a was downexpressed in 786-O cells, and examined transfected efficiency. According to functional assay, overexpression of miR-125a inhibited cell migration and cell invasion, but no obvious effect was observed on cell proliferation. The luciferase activity assay showed that miR-125a could directly target STAT3 3'-untranslated regions. Meanwhile, quantitative polymerase chain reaction (qPCR) assay and Western blot analysis demonstrated that miR-125a could inhibit STAT3 expression at both messenger RNA and protein levels. Furthermore, the combination sites between STAT3 and HAS1 were predicted by prediction of transcription factor binding sites database analysis. The expression of STAT3 was correlated with HAS1 expression, exemplified by the same tendency detected by qPCR assay. Taken together, our results preliminarily demonstrate that miR-125a could constrain cell migration, invasion, and regulate HAS1 expression in RCC cells by targeting STAT3. It is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in RCC.

Low expression of miR125a-5p predicts sensitivity to sorafenib by upregulating STAT3 and HTATIP2 in hepatocellular carcinoma

“…It has been reported in several cancers that the antitumor effect of miR125a-5p is associated to STAT3 inhibition. For example, miR-125a promotes paclitaxel sensitivity through inhibiting STAT3 expression in cervical cancer [22], gastric cancer cells [23], and renal cancer [24]. The current study con rmed that STAT3 pathway was down-regulated by miR125a-5p, as revealed by IPA analysis, website prediction, luciferase reporter assay, PCR and western blotting.…”

Glycosylation in Renal Cell Carcinoma: Mechanisms and Clinical Implications

“…In recent years, an increasing number of researchers have focused on the relationship between tumorigenesis and HAS1 and showed the role of HAS1 in the growth of RCC and other malignant tumors [ 92 ]. The results of Mao-Kun Sun et al showed that miR-125a could inhibit RCC cell migration and invasion by targeting STAT3 to regulate the expression of HAS1 [ 93 ]. In summary, the abnormal expression of PGs in tumor cells might be used as a marker for cancer progression and patient.…”

Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

“…3 A). While there are other HAS enzymes (HAS2 and HAS3), HAS1 has been shown to be associated with cell migration and invasion in renal carcinoma cells [26] . The cells were subcloned by serial dilution in 96-well plates, and single colonies were subcultured.…”