In summary, our results reveal that the upregulation of miR-214 as a frequent event in osteosarcoma contributes to radioresistance by regulating the PHLDA2/Akt pathway.
Importantly, dysregulation in miR-214 expression is associated with pathological bone conditions such as osteoporosis, osteosarcoma, multiple myeloma, and osteolytic bone metastasis of breast cancer.
The MG63, Saos‑2 and U2OS cells were infected with the hsa‑mir‑214 lentivirus for 48 h, and the levels of miR‑214 were significantly upregulated in the human osteosarcoma cancer cells.
The results of our meta-analysis revealed that elevated levels of miR-21, miR-214, miR-29, miR-9 and miR-148a were associated with poor prognosis in osteosarcoma.
MicroRNA-214 and -126 were prognostic predictors in 2 groups (adenocarcinoma and non-epithelial tumours except for osteosarcoma) and 3 groups (epithelial tumours, adenocarcinoma, and melanoma), respectively.
Our findings define a negative feedback pathway in control of WWOX and miR‑214‑3p expression, thus providing novel molecular targets for the treatment of osteosarcoma.
Together, these data indicated that miR‑214 acts as an oncogenic miRNA and may contribute to the progression, and metastasis of OS, suggesting that miR‑214 may be a potential novel diagnostic and therapeutic target of OS.
Furthermore, ectopic expression of miR‑214 markedly promoted osteosarcoma development in a subcutaneous xenotransplantation model in BALB/c athymic nude mice.
High miR-214 expression occurred more frequently in osteosarcoma tissues with large tumor size (P = 0.01), positive metastasis (P = 0.001) and poor response to pre-operative chemotherapy (P = 0.006).
Taken together, our data provide compelling evidence that miR-214 functions as an onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of LZTS1.