miR-135a Reduces Osteosarcoma Pulmonary Metastasis by Targeting Both BMI1 and KLF4
Chenglong Chen1,2, Xingjia Mao3, Caitong Cheng3
1Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.
Abstract:
Because of the modest response rate after surgery and chemotherapy, treatment of osteosarcoma (OS) remains challenging due to tumor recurrence and metastasis. miR-135a has been reported to act as an anticarcinogenic regulator of several cancers. However, its expression and function in osteosarcoma remain largely unknown. Here, we reported that abridged miR-135a expression in OS cells and tissues, and its expression is inversely correlated with the expression of BMI1 and KLF4, which are described as oncogenes in several cancers. Ectopic expression of miR-135a inhibited cell invasion and expression of BMI1 and KLF4 in OS cells. In vivo investigation confirmed that miR-135a acts as a tumor suppressor in OS to inhibit tumor growth and lung metastasis in xenograft nude mice. BMI1 and KLF4 were revealed to be direct targets of miR-135a, and miR-135a had a similar effect as the combination of si-BMI1 and si-KLF4 on inhibiting tumor progression and the expression of BMI1 and KLF4 in vivo. Altogether, our results demonstrate that the targeting of BMI1/KLF4 with miR-135a may provide an applicable strategy for exploring novel therapeutic approaches for OS.
Insights
MicroRNA-135a (miR-135a) acts as a tumor suppressor in osteosarcoma (OS) by inhibiting cell invasion and metastasis. Targeting BMI1 and KLF4 with miR-135a offers a potential therapeutic strategy for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Osteosarcoma (OS) treatment faces challenges due to modest response rates, leading to tumor recurrence and metastasis.
- MicroRNA-135a (miR-135a) is known as an anticarcinogenic regulator in various cancers, but its role in OS is largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of miR-135a in osteosarcoma.
- To determine the relationship between miR-135a, BMI1, and KLF4 in OS.
- To evaluate the therapeutic potential of miR-135a in OS.
Main Methods:
- Assessed miR-135a expression in OS cells and tissues.
- Performed ectopic expression of miR-135a in OS cells to analyze effects on invasion and oncogene expression.
- Conducted *in vivo* xenograft studies in nude mice to evaluate tumor growth and metastasis inhibition.
- Identified direct targets of miR-135a and compared its effects with targeting BMI1 and KLF4.
Main Results:
- Abridged miR-135a expression was observed in OS cells and tissues, inversely correlated with oncogenes BMI1 and KLF4.
- Ectopic miR-135a expression suppressed OS cell invasion and reduced BMI1/KLF4 levels.
- *In vivo* studies confirmed miR-135a's tumor suppressor role, inhibiting tumor growth and lung metastasis.
- BMI1 and KLF4 were identified as direct targets of miR-135a.
Conclusions:
- miR-135a functions as a tumor suppressor in osteosarcoma.
- Targeting the miR-135a/BMI1/KLF4 pathway presents a promising novel therapeutic strategy for osteosarcoma.
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