MicroRNA-543 inhibits proliferation, invasion and induces apoptosis of glioblastoma cells by directly targeting ADAM9

Abstract

Glioma is the most common type of malignant brain tumor in humans and accounts for 81% of all malignant brain tumor cases in adults. The abnormal expression of microRNAs (miRs) has been reported to be important in the formation and progression of various types of human cancer, including glioblastoma (GBM). Therefore, studies into the expression, and roles of microRNAs as diagnostic and prognostic markers, as well as their therapeutic value for patients with GBM are warranted. The expression and roles of miR‑543 have been reported in several types of human cancer. However, the role of miR‑543 in GBM remains unclear. In the current study, the expression pattern of miR‑543 in GBM, the effects of miR‑543 on GBM cells and the underlying molecular mechanism was determined. The results of the present study demonstrated that miR‑543 was significantly downregulated in GBM tissue samples and cell lines. Furthermore, the upregulation of miR‑543 inhibited GBM cell proliferation and invasion, as well as promoted cell apoptosis. In addition, a disintegrin and metalloproteinase 9 (ADAM9) was identified to be a direct target gene of miR‑543. Furthermore, ADAM9 was significantly upregulated in GBM tissue samples and its expression was inversely correlated with miR‑543 expression in GBM tissue, suggesting that miR‑543 downregulation may contribute to ADAM9 upregulation in GBM. Finally, the results of the rescue experiment indicated that ADAM9 overexpression significantly reversed the effects of miR‑543 on the proliferation, invasion and apoptosis of GBM cells, suggesting that miR‑543 serves as a tumor suppressor in GBM through ADAM9 regulation. Overall, these findings indicate that the miR‑543/ADAM9 signaling pathway may provide as a potential therapeutic strategy for GBM.

miR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T)

“…Here, we focused on the part that miR-543 takes in breast cancer progression, attempting to provide additional new information regarding biotarget therapy for breast cancer. Previously, lower miR-543 expression was reported in endometrial cancer [ 30 ] and glioma [ 31 ], which is in accordance with the present observation that miR-543 displayed a reduced level in breast cancer progression. In the present study, functionally, miR-543 acted as an anti-tumor miRNA in breast cancer and participated in regulating cell viability, proliferation, migration, and invasion.…”

MicroRNA‑574‑3p inhibits the malignant behavior of liver cancer cells by targeting ADAM28

“…Based on the involvement of ADAMs in cancer, ADAMs can be regulated by miRNAs to modulate the progression of tumorigenesis (37)(38)(39)(40)(41)(42)(43)(44)(45). A previous study revealed that miR-552 targets ADAM28 in colorectal cancer and enhances the metastasis of cancer cells (26).…”

Non-Coding RNAs and Brain Tumors: Insights Into Their Roles in Apoptosis

“…It can promote apoptosis by decreasing ZBTB20 in glioblastoma cell ( Liu et al, 2018a ). There is a downregulation of miR-543 in glioblastoma and its upregulation can induce apoptosis by targeting ADAM9 ( Ji et al, 2017 ). MiR-152-3p affected the apoptosis of glioblastoma cells via NF2 overexpression ( Sun et al, 2017 ).…”