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.

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.

Sun M ，Guo S ，Yao J ，Xiao Y ，Sun R ，Ma W ，Dong Z ... -  《-》

miR-125a regulates HAS1 and inhibits the proliferation, invasion and metastasis by targeting STAT3 in non-small cell lung cancer cells.

MicroRNA-125a (miR-125a) is related to the occurrence, development, and prognosis of various cancers according to relevant reports. However, its function role and mechanism in non-small cell lung cancer (NSCLC) is yet to be explored. Herein, we investigated the role and preliminary mechanism of miR-125a in NSCLC. First, miR-125a was noticeably downregulated in NSCLC tissues in contrast to adjacent normal tissues through the real-time quantitative polymerase chain reaction (RT-qPCR) assay. The inverted result was observed on the STAT3 and HAS1 expressions. Moreover, miR-125a was expressed at highest level in A549 among four human NSCLC cell lines. Second, functional studies indicated miR-125a restrained proliferation, invasion, migration, metastasis, and advocated apoptosis of NSCLC cells, but had no obvious effect on cell cycle. Next, results indicated that a target of miR-125a was STAT3 on the basis of prediction and confirmation by the dual-luciferase reporter assay. RT-qPCR and Western blot assays displayed that miR-125a overexpression conspicuously constrained STAT3 expression at messenger RNA and protein levels. Finally, the binding between HAS1 promoter region and STAT3 was predicted by PROMO database analysis and verified by chromatin immunoprecipitation assay, suggesting that STAT3 was bound with the HAS1 promoter regions. STAT3 overexpression exerted positive effects on HAS1 expression at protein and mRNA levels. Additionally, HAS1-related functional studies illustrated HAS1 pronouncedly suppressed the proliferative, invasive, and migratory potential of NSCLC cells in vitro. Collectively, our findings demonstrated that miR-125a prohibited the proliferation, invasion, and migration of NSCLC cells by HAS1 expression reduction as a result of inhibiting STAT3 expression in NSCLC. This study indicated that miR-125a might be of potential or value for NSCLC treatment.

Huang H ，Huang J ，Yao J ，Li N ，Yang Z ... -  《-》

MicroRNA-125a-5p plays a role as a tumor suppressor in lung carcinoma cells by directly targeting STAT3.

Zhong L ，Sun S ，Shi J ，Cao F ，Han X ，Chen Z ... -  《-》

MicroRNA-363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2-signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene.

Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA-363 (miR-363) affects the development of RCC via the Janus tyrosine kinases (JAK2)-signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR-363 mimic, miR-363 inhibitor, or small interfering RNA against GHR to determine the influence of miR-363 on the expression of GHR and JAK2-STAT3 axis-related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), wound-healing, and Transwell assays. The results revealed reduced miR-363 expression and elevated GHR expression in RCC. It was also found that miR-363 altered the activation of the JAK2-STAT3 axis through the inhibition of GHR. Cells treated with the miR-363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR-363. These results implicated that the overexpression of miR-363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2-STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC.

Zhu J ，Zhu DQ ，Zhang Y ，Liu QM ，Wang PC ，Li HZ ，Ma X ，Zhang X ... -  《-》

MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3.

Fan Z ，Cui H ，Xu X ，Lin Z ，Zhang X ，Kang L ，Han B ，Meng J ，Yan Z ，Yan X ，Jiao S ... -  《Oncotarget》