MicroRNA-18a inhibits cell growth and induces apoptosis in osteosarcoma by targeting MED27

Abstract

Osteosarcoma (OS) is a common malignant primary bone tumor and patients with OS are known to have a poor response to chemotherapy. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules (approximately 22 nucleotides in length) and they have recently become a topic for research as regards their role in cancer therapeutics. Previous studies have reported miR‑18a expression in patients with OS is significantly decreased compared with that in normal adjacent tissue. miR‑18a belongs to the miR‑17‑92 cluster encoded by the host gene MIR17HG. However, the detailed role of miR‑18a in OS remains to be determined. In this study, we demonstrated that miR‑18a mimics inhibited MG63 and Saos‑2 cell viability and migration. In addition, flow cytometry assay revealed that miR‑18a induced OS cell apoptosis. Western blot analysis indicated that the expression levels of Bcl‑2 and p‑Akt were downregulated, while the levels of cleaved caspase‑3 and Bax proteins were upregulated by miR‑18a. Moreover, we demonstrated that mediator complex subunit 27 (MED27) was the target of miR‑18a through dual luciferase assay. Finally, data from in vivo experiments indicated that tumor growth in mice was significantly suppressed by miR‑18a mimics, accompanied by a decrease in the percentage of Ki67-positive cells, and by the downregulation in MED27 and p‑Akt protein expression levels. The findings of the present study may aid in the clarification of the function of miR‑18a, particularly as regards its role in the regulation of OS cell apoptosis, and indicate that MED27 may be a potential novel therapeutic target in the treatment of OS.

CRSP8 promotes thyroid cancer progression by antagonizing IKKα-induced cell differentiation

“…Thus, compared with the direct transcriptional regulation approved in our study, such indirect regulation might still need further exploration. Besides, CRSP8 was recently reported to be reversely regulated by miR-18a, which belongs to the miR-17-92 cluster, as its direct target in osteosarcoma [44], implying the possibility that miR-18a might similarly regulate CRSP8 in thyroid cancer cells. Nevertheless, considering earlier reports that all members of miR-17-92 cluster except miR-17-3p were overexpressed and partial play oncogenic function in ATC [45], the hypothesis mentioned above seems not valid.…”

Identification of a three‐miRNA signature as a novel potential prognostic biomarker in patients with clear cell renal cell carcinoma

“…Some studies reported miR‐18a to have a proangiogenic function during tumor angiogenesis . miR‐18a can inhibit cell growth and induces apoptosis through targeting MED27 gene and inhibiting its expression, but some research showed miR‐18a plays a key role in tumor suppression through targeting TBPL1 gene . miR‐223 can promote cancer cell invasion and metastasis by downregulating p120, thereby reducing intercellular adhesion, promoting RhoA activity, and activating β‐catenin signaling .…”

LINC00899 Promotes Osteogenic Differentiation and Alleviates Osteoporosis via Targeting miR-374a to Regulate RUNX2

“…MicroRNAs (miRNAs) are short non-coding RNAs with a length of ~ 22 nt, which act as vital regulators in biological processes, such as cell proliferation and differentiation [12]. miRNA has been reported to be involved in osteoporosis by binding the 3'-'UTR of their target mRNA.…”