MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway

Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues. miR-181a-5p mimic significantly promoted, while miR-181a-5p inhibitor blocked the proliferation, colony formation, migration, invasion, and cell cycle progression of osteosarcoma cells. Mechanistically, miR-181a-5p bound to the 3 ′ -untranslational region of phosphatase and tensin homolog (PTEN) and reduced its protein expression, thereby activating protein kinase B (PKB/AKT) pathway. Either PTEN overexpression or AKT inhibition notably blocked the tumor-promoting effects of miR-181a-5p. Moreover, we observed that miR-181a-5p mimic further inhibited growth of human osteosarcoma cells in the presence of adriamycin or cisplatin. Overall, miR-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway and it is a promising therapeutic target to treat osteosarcoma.

Exosomal miR‐181a‐5p derived from SAOS‐2 cells promotes macrophages M2 polarization by targeting RORA

“…13,26 For instance, miR-181a-5p was known to be upregulated in osteosarcoma and play as a tumorpromoting role via accelerating cell proliferation and decreasing cell apoptosis. 15 Consistently, the results of the present study showed Interestingly, it was also reported that cancer-associated fibroblast, another major cell in TME, delivered exosomal miR-181a-5p to a lung cancer cell to promote cell apoptosis. 13 From these results, it could be inferred that miR-181a-5p play as a critical regulator in the cross talk of tumor cells and TME.…”

“…It was demonstrated that miR‐181a‐5p acted as an oncogene in multiple cancers 13,26 . For instance, miR‐181a‐5p was known to be upregulated in osteosarcoma and play as a tumor‐promoting role via accelerating cell proliferation and decreasing cell apoptosis 15 . Consistently, the results of the present study showed that miR‐181a‐5p was upregulated in osteosarcoma tissues and cell lines.…”

“…Zang et al indicated that miR‐181a‐5p was overexpressed in osteosarcoma and could promote proliferation and metastasis 14 . Moreover, it was also highlighted that miR‐181a‐5p was upregulated in osteosarcoma tissue and cell lines, and high miR‐181a‐5p expression was correlated with poor prognosis 15 . However, the role of miR‐181a‐5p in osteosarcoma is not clear.…”

“…14 Moreover, it was also highlighted that miR-181a-5p was upregulated in osteosarcoma tissue and cell lines, and high miR-181a-5p expression was correlated with poor prognosis. 15 However, the role of miR-181a-5p in osteosarcoma is not clear. Therefore, it is necessary to explore the specific roles of miR-181a-5p in osteosarcoma and TAMs polarization.…”

A prognostic model for cervical cancer based on ferroptosis-related genes

“…The miR-181a-5p can relieve the downstream inhibition of CARM1, thus inactivating the type 1 interferon response in the LUAD and LUSC (28). It also facilitates tumor progression through NDRG2-induced activation of the PTEN/AKT signaling pathway of breast cancer (29) and osteosarcoma (30). More importantly, CCAT1 can promote cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis (31).…”