MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1

Abstract

Abstract. MicroRNAs (miRs) have been demonstrated to serve important roles in the development and progression of human cancer, primarily through the direct targeting of oncogenes or tumor suppressors. It has been previously suggested that miR-126 may be associated with endometrial cancer (EC). However, the exact role of miR-126 in the migration and invasion of EC cells has not yet been studied. The present study demonstrated that the expression of miR-126 was significantly decreased in EC tissues when compared with matched normal adjacent tissues. The current study reverse transcriptionquantitative polymerase chain reaction was performed in order to examine the expression level of miR-126. Wound healing and transwell assays were used to examine cell migration and invasion. A luciferase reporter assay was used to determine the targeting relationship and western blotting assay was performed to detect the protein expression. Furthermore, the overexpression of miR-126 significantly inhibited EC SKOV3 cell migration and invasion. Molecular mechanism investigation established that insulin receptor substrate 1 (IRS1) functioned as a direct miR-126 target, and its expression was negatively regulated by miR-126 at a post-transcriptional level in the SKOV3 cells. Additionally, the overexpression of IRS1 reversed the inhibitory effect of miR-126 overexpression on SKOV3 cell migration and invasion. In conclusion, the current study demonstrated that miR-126 inhibited EC cell migration and invasion, at least partially through the direct targeting of IRS1, suggesting that miR-126 may aid the treatment of EC metastasis.

RETRACTED: Long non‐coding RNA CRNDE sponges miR‐384 to promote proliferation and metastasis of pancreatic cancer cells through upregulating IRS1

“…Wang et al showed that IRS1 expression was significantly boosted in both breast cancer cell lines and tissues, and overexpression of IRS1 could reverse miR‐195‐mediated repression of tumour cell proliferation; moreover, miR‐195 inhibited tumour angiogenesis via IRS1. Zhao et al indicated that miR‐126 inhibited endometrial cancer cell migration and invasion through directly targeting IRS1. In addition, it has been reported that downregulation of IRS1 could inhibit the activation of AKT signalling pathway, which is implicated in tumorigenesis as well as development of osteosarcoma .…”

MicroRNA‑409 may function as a tumor suppressor in endometrial carcinoma cells by targeting Smad2

“…For example, miRNA-505 functions as a tumor suppressor in endometrial cancer by targeting transforming growth factor (TGF)-α, whereas, miR-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1. In addition, miR-490-3P may act as a suppressor in the tumorigenesis and progression of endometrial cancer by targeting TGF-α (16,20,21). However, current understanding of the aberrant expression and potential roles of miRNAs remains limited.…”

Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development of hepatocellular carcinoma

“…miRNAs belongs to a class of non-coding small RNAs that comprise 18-23 nucleotides (Reddy, 2015). Previous studies have indicated that many miRNAs play an important role in carcinogenesis by regulating the expression of oncogenes and tumor suppressors (Zhang et al, 2015c;Zhao et al, 2016). Polymorphisms in miRNAs can alter the expression of proteins, thereby changing their function Song et al, 2016).…”