MicroRNA‑126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial‑to‑mesenchymal transition and ERK/MAPK signaling pathway

Abstract

Ovarian cancer (OC) is a common gynecological malignant carcinoma worldwide. Accumulating research has revealed that multiple microRNAs (miRNAs) are abnormally expressed at different levels in various malignancies, playing vital roles in tumorigenesis. This study investigated the regulatory functions and potential mechanism of miR-126 in OC proliferation, invasion and migration. It was found that miR-126 was prominently downregulated in OC. Moreover, the decrease of miR-126 promoted the aggressive phenotypes and indicated poor prognosis of OC patients. Functional assays demonstrated that restoration of miR-126 dramatically repressed OC cell proliferation, migration and invasion. Furthermore, luciferase reporter assay was conducted to verify putative binding sites of miR-126 in the epidermal growth factor-like domain 7 (EGFL7) 3 untranslated region (3′UTR), indicating that EGFL7 was a target gene of miR-126 in OC cells. It was further discovered that miR-126 exerts its function on regulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT) in OC cells. The above findings suggested that miR-126 served as a cancer suppressor in OC, suggesting a promising application of miR-126 in the clinical diagnosis and therapeutics of OC.

MicroRNA‑126 expression in the peripheral white blood cells of patients with breast and ovarian cancer is a potential biomarker for the early prediction of cancer risk in the carriers of methylated BRCA1

“…These results agree with previously reported data, where it was shown that the frequency of BRCA1 methylation in WBCs was higher in patients with OC than in controls and that it was associated with risk for HGSOC (22). miR-126 is downregulated in tumor tissues compared with that in normal adjacent tissues in several cancer types, including BC, OC and colorectal cancer, and this decrease is associated with higher malignancy tumor grade and metastasis (31,32,38). The restoration of miR-126 has been demonstrated to inhibit metastasis properties in these cancer types (32,38).…”

“…miR-126 is downregulated in tumor tissues compared with that in normal adjacent tissues in several cancer types, including BC, OC and colorectal cancer, and this decrease is associated with higher malignancy tumor grade and metastasis (31,32,38). The restoration of miR-126 has been demonstrated to inhibit metastasis properties in these cancer types (32,38).…”

“…The patients with DCIS BC have a lower level of tissue and circulating miR-126 compared with normal adjacent tissue and healthy controls, respectively (31). Furthermore, downregulation of miR-126 is associated with aggressive OC with a poor prognosis (32,33). However, another study has observed upregulation of miR-126 in OC (34).…”

ARHGEF19 promotes the growth of breast cancer in vitro and in vivo by the MAPK pathway

“…For example, F1012-2 induced DNA damage response via targeting the MAPK pathway in breast cancer [24]. Another study showed that EGFL7 regulated the growth of breast cancer cells via the MAPK pathway [25]. These studies, together with our findings, confirmed that the MAPK pathway could serve as a promising target of breast cancer.…”

MiR-126 Suppresses Colitis-Associated Colorectal Cancer by Regulating Crosstalk Between Epithelium Cells and Macrophages via CXCL12

“…We previously demonstrated that miR-126 acts as a tumor suppressor via the down-regulation of CXCR4 and the inhibition of the RhoA/ROCK pathway in colon cancer [9]. Other researchers reported that miR-126 exerts antitumor functions in various types of cancers, such as ovarian cancer, liver cancer, gastric cancer, and non-small cell lung cancer [10,11]. MiR-126 is also involved in the regulation of in ammatory events [12].…”