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MicroRNA-767-5p promotes metastasis but improves chemotherapeutic and radiotherapeutic sensitivity of osteosarcoma
Xuelian Luo1,2, Xiaoyan Dai3, Qingsong Wei3
1Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Abstract:
The aim of this study was to explore the role of microRNA-767-5p (miR-767-5p) in regulating the osteosarcoma (OS) prognosis, metastasis and sensitivity to chemotherapeutic and radiotherapeutic sensitivity. We observed that miR-767-5p expression in the specimens of patients with metastatic OS was higher than in healthy individuals and was also negatively correlated with the overall survival of patients with OS. Functional assays (CCK-8, transwell, colony formation) and a tumor xenograft model demonstrated that miR-767-5p over-expression in both U2OS and 143B OS cell lines promoted cell invasion and migration without affecting proliferation, whereas its knockdown had opposite effects. Notably, miR-767-5p over-expression enhanced the sensitivity of both U2OS and 143B cells to chemotherapy or radiotherapy. Combing target gene prediction, RNA-sequencing and overall survival analysis, we identified aryl hydrocarbon receptor (AHR) as the potential target gene of miR-767-5p. Luciferase assay confirmed that miR-767-5p promoted the 3'-UTR activity of AHR through direct binding. Strikingly, AHR over-expression in both U2OS and 143B cells suppressed invasion, migration while reduced therapeutic sensitivity to chemotherapy and radiotherapy-thereby reversing miR-767-5p's phenotypic impact. Therefore, this study suggested that miR-767-5p promotes OS metastasis but improves its sensitivity to radiotherapy and chemotherapy.
Insights
MicroRNA-767-5p (miR-767-5p) promotes osteosarcoma metastasis but enhances sensitivity to chemotherapy and radiotherapy. Targeting miR-767-5p could offer new therapeutic strategies for osteosarcoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a primary bone malignancy with poor prognosis, particularly in metastatic cases.
- MicroRNAs play crucial roles in cancer development and progression, acting as potential therapeutic targets.
Purpose of the Study:
- To investigate the role of microRNA-767-5p (miR-767-5p) in osteosarcoma (OS) prognosis, metastasis, and response to therapy.
- To identify the molecular mechanisms underlying miR-767-5p's function in OS.
Main Methods:
- Analysis of miR-767-5p expression in OS patient specimens and correlation with survival.
- In vitro functional assays (CCK-8, transwell, colony formation) in OS cell lines (U2OS, 143B).
- Tumor xenograft models, RNA-sequencing, luciferase assays, and target gene identification (Aryl hydrocarbon receptor - AHR).
Main Results:
- miR-767-5p expression was elevated in metastatic OS and negatively correlated with patient survival.
- Overexpression of miR-767-5p promoted OS cell invasion and migration, while knockdown inhibited these processes.
- miR-767-5p overexpression enhanced OS cell sensitivity to chemotherapy and radiotherapy.
- Aryl hydrocarbon receptor (AHR) was identified as a direct target of miR-767-5p; AHR overexpression reversed miR-767-5p's effects on metastasis and therapeutic sensitivity.
Conclusions:
- miR-767-5p promotes osteosarcoma metastasis.
- miR-767-5p enhances osteosarcoma sensitivity to chemotherapy and radiotherapy.
- The miR-767-5p/AHR axis represents a potential therapeutic target for osteosarcoma treatment.
