miR‑186 functions as a tumor suppressor in osteosarcoma cells by suppressing the malignant phenotype and aerobic
Qianren Xiao1, Zhihui Wei1, Yunyun Li2
1Department of Orthopedics, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.
Abstract:
Osteosarcoma (OS) is the most common primary bone malignancy among children and adolescents. Deregulation of microRNAs has been well documented in OS, while the putative effects of miR‑186 have not been identified yet. In the present study, we assessed the expression of miR‑186 in a cohort of 40 OS tissues and explored its effects on OS cells. As expected, miR‑186 was suppressed in OS tissues compared with relative normal tissues. Overexpression of miR‑186 inhibited cell proliferation, arrested the cell cycle progression and suppressed the cell invasion of the HOS and U2 OS cell lines. These results indicated the tumor‑suppressive role of miR‑186 in OS. Among the target genes of miR‑186, we found that pituitary tumor transforming gene 1 (PTTG1) may be a target gene of miR‑186 in OS and that the overexpression of PTTG1 could partially abolish miR‑186‑mediated suppressive effects on OS cells. Aerobic glycolysis is the major way of energy supply and is one of the characteristic phenotypes of tumor cells. In addition, we found that overexpression of miR‑186 significantly suppressed the expression of hypoxia‑inducible factor 1 (HIF‑1) and inhibited the glucose uptake and lactate production of OS cells. Collectively, our findings demonstrated that miR‑186 functions as a tumor suppressor in OS cells partially by targeting PTTG1 and that HIF‑1‑mediated suppression of aerobic glycolysis may be also involved in its suppressive effects.
Insights
MicroRNA-186 (miR-186) acts as a tumor suppressor in osteosarcoma (OS). It inhibits cancer cell growth and invasion, partly by targeting PTTG1 and suppressing aerobic glycolysis via HIF-1.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a prevalent pediatric bone cancer.
- MicroRNA deregulation is common in OS, but miR-186's role is unknown.
Purpose of the Study:
- To investigate miR-186 expression and function in OS.
- To identify miR-186 targets and pathways involved in OS.
Main Methods:
- Assessed miR-186 expression in 40 OS tissues.
- Overexpressed miR-186 in HOS and U2 OS cell lines.
- Analyzed effects on cell proliferation, cell cycle, invasion, PTTG1, HIF-1, glucose uptake, and lactate production.
Main Results:
- miR-186 was suppressed in OS tissues.
- miR-186 overexpression inhibited OS cell proliferation, cell cycle progression, and invasion.
- miR-186 targeted PTTG1 and suppressed HIF-1, reducing aerobic glycolysis.
Conclusions:
- miR-186 functions as a tumor suppressor in osteosarcoma.
- Its effects involve targeting PTTG1 and inhibiting HIF-1-mediated aerobic glycolysis.
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