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lncRNA JPX modulates malignant progress of osteosarcoma through targeting miR-33a-5p and PNMA1 regulatory loop
Wei Xiong1, Dan Liu1, Xi Chen1
1Department of General Vascular Surgery, Wuhan No.1 Hospital & Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China.
Abstract:
Osteosarcoma (OS) is a common type of bone tumor, present worldwide, that has distal metastasis ability. Although continuous development in cancer therapy has taken place, there are still no effective metastasis-curbing strategies for OS available. Hence, a better understanding of the biological characteristics and molecular mechanisms of OS carcinogenesis is urgently needed. Long noncoding RNAs (lncRNAs) have captured great interest among cancer scientists with considerable potential implications for cancer treatment. In this study, we found that lncRNA JPX was up-regulated in OS tissues and cells. We subsequently examined the functional role of JPX in OS cells through knocked-down JPX by using siRNA. JPX down-regulation was observed to suppress OS cell proliferation, migration and invasion. Furthermore, it was verified that JPX acts as a sponge for miR-33a-5p, and that JPX regulated OS cell proliferation, migration and invasion through miR-33a-5p. Moreover, down-regulation of miR-33a-5p in OS contributed to PNMA1 upregulation, and PNMA1 depletion inhibited OS cell proliferation, migration and invasion in vitro. Taken together, our data support an important role of JPX in regulating OS cell proliferation, invasion and migration that highlights JPX may be a potential therapeutic target for OS.
Insights
Long noncoding RNA JPX promotes osteosarcoma (OS) progression and metastasis. Targeting JPX could offer a new therapeutic strategy for this bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a prevalent bone tumor with high metastatic potential.
- Current cancer therapies lack effective strategies to curb OS metastasis.
- Understanding OS carcinogenesis mechanisms is crucial for developing new treatments.
Purpose of the Study:
- Investigate the role of long noncoding RNA JPX (lncRNA JPX) in osteosarcoma.
- Elucidate the molecular mechanisms underlying JPX's function in OS progression.
Main Methods:
- Quantitative real-time PCR to measure lncRNA JPX expression in OS tissues and cells.
- siRNA-mediated knockdown of JPX to assess its functional impact.
- In vitro assays to evaluate cell proliferation, migration, and invasion.
- MiRNA sponge assays to determine interactions between JPX and miR-33a-5p.
- Western blotting to assess protein expression levels.
Main Results:
- lncRNA JPX was significantly upregulated in OS tissues and cells.
- JPX knockdown suppressed OS cell proliferation, migration, and invasion.
- JPX functioned as a molecular sponge for miR-33a-5p, mediating its effects on OS cells.
- Downregulation of miR-33a-5p led to PNMA1 upregulation, which promoted OS cell proliferation, migration, and invasion.
Conclusions:
- lncRNA JPX plays a critical role in promoting osteosarcoma cell proliferation, migration, and invasion.
- The JPX/miR-33a-5p/PNMA1 axis is a key regulatory pathway in OS.
- lncRNA JPX represents a potential therapeutic target for osteosarcoma treatment.
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