MiR‐193a‐3p and miR‐224 mediate renal cell carcinoma progression by targeting alpha‐2,3‐sialyltransferase IV and the phosphatidylinositol 3 kinase/Akt pathway

Abstract

Tumor metastasis is a major cause of cancer-related death in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been widely known to modulate proliferation invasion, metastasis, and apoptosis of cancer cells. In this study, we aimed to investigate the function and novel target of miR-193a-3p and miR-224 in RCC. The levels of miR-193a-3p and miR-224 were significantly increased in RCC tissues and RCC cell lines. Alpha-2,3-Sialyltransferase IV (ST3GalIV) was highly expressed in adjacent nontumor tissues and human normal proximal tubular cell line HK-2 compared to RCC tissues and cell lines. ST3GalIV expression was negatively correlated with miR-193a-3p and miR-224. Further analysis indicated that miR-193a-3p and miR-224 directly targeted ST3GalIV. MiR-193a-3p and miR-224 increased cell proliferation and migration by directly inhibiting ST3GalIV, and this effect was reversed by co-transfection with ST3GalIV in vitro. Overexpression of miR-193a-3p and miR-224 increased RCC cell proliferation in vivo. Furthermore, the phosphatidylinositol 3 kinase (PI3K)/Akt pathway was mediated by miR-193a-3p and miR-224 in RCC cell lines. Collectively, these results suggested that miR-193a-3p and miR-224 played an important role in regulation of RCC by targeting ST3GalIV via PI3K/Akt pathway.

Circulating Non-coding RNAs in Renal Cell Carcinoma—Pathogenesis and Potential Implications as Clinical Biomarkers

“…This indicates the importance of exosomal miRNAs in cancer progression (Fujii et al, 2017;Kulkarni et al, 2019). Furthermore, miR-224 was shown to influence RCC progression by directly targeting alpha-2,3-sialyltransferase IV and impacting the PI3K/AKT pathway (Pan Y. et al, 2018).…”

“…However, since corresponding tissue samples were not analyzed in the study, conclusions on the altered expression levels in RCC tissue and their potential reflection in serum miRNA expression and additional involvement in ccRCC pathogenesis cannot be drawn. As for miR-193a-3p, it was shown to target the tumor suppressor phosphatase and tensin homolog (PTEN) and mediate the PI3K/Akt pathway, thereby promoting RCC cell growth and progression ( Liu L. et al, 2017 ; Pan Y. et al, 2018 ). miR-572 likewise represents an oncomir in RCC pathogenesis by enhancing proliferation and invasion and inhibiting tumor cell apoptosis by suppressing NF2/Hippo signaling ( Guan et al, 2018 ; Pan et al, 2018a ).…”

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

“…To a further extent, PI3K/AKT/mTOR is identified as a highly enriched pathway in translocation RCC with TFE3 fusion (TFE3-tRCC) by miRNA microarray analysis [258]. Besides that PIK3R1 regulates EMT and stem-like phenotype of RCC cells through the AKT/GSK3β/CTNNB1 pathway [259], FoxO, PKCε, TPD52, NOTCH1, ETS2, miR-19b, -122, -182, -193a-3p, -195, and -224, as well as LncRNA MALAT1, TP73-AS1 and HOTTIP modulate proliferation, apoptosis, invasion, metastasis, or EMT via PI3K/ AKT pathway [260][261][262][263][264][265][266][267][268][269][270][271][272]. However, only a few of clinical trials of PI3K/AKT inhibitors in touch try to offer hope for KC patients (Tables 2 and 3).…”

Stabilization of miRNAs in esophageal cancer contributes to radioresistance and limits efficacy of therapy

“…miR-193a-3p located on chromosome 17q11.2 has been implicated in a number of roles in different types of cancers. For example, it has been found to act as a tumor-suppressor in gastric cancer [79], renal cell carcinoma [80], hepatocellular carcinoma [81], and ovarian cancer [82], whereas it has an oncogenic role in esophageal squamous cell carcinoma [18].…”