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Inhibiting proliferation and metastasis of osteosarcoma cells by downregulation of long non-coding RNA colon cancer-associated transcript 2 targeting microRNA-143.

ABSTRACT: Osteosarcoma is a malignant bone tumor, which has a high incidence in children and adolescents. However, the pathogenesis of osteosarcoma remains unclear. Long noncoding RNA (lncRNA) is a new potential therapeutic target and diagnostic biomarker for osteosarcoma. Hence, the present study aimed to explore the effect of lncRNA colon cancer-associated transcript (CCAT2) on osteosarcoma and its potential underlying mechanisms. For this purpose, the proliferation of osteosarcoma cells was measured using the CCK-8 assay. The scratch-wound and cell invasion assays were used to determine the migration and invasion of osteosarcoma cells, respectively. LncRNA CCAT2 and microRNA (miR)-143 binding sites were identified by the dual-luciferase reporter assay. RNA and protein expression levels were detected by reverse-transcription quantitative PCR and western blotting, respectively. Downregulation of lncRNA CCAT2 inhibited the proliferation, migration, and invasion of osteosarcoma cells. The findings also revealed that miR-143 bound directly to lncRNA CCAT2. The expression of miR-143 was upregulated by the knockdown of lncRNA CCAT2. Downregulation of the FOS-like antigen 2 was also observed after knockdown of lncRNA CCAT2. The function of lncRNA CCAT2 in osteosarcoma cells was attenuated by co-transfection with anti-miR-143 oligodeoxyribonucleotide. In conclusion, downregulation of lncRNA CCAT2 inhibited the proliferation and metastasis of osteosarcoma cells by targeting miR-143. lncRNA CCAT2 was identified as a potential target for osteosarcoma treatment.

SUBMITTER: Bi F

PROVIDER: S-EPMC7882883 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Inhibiting proliferation and metastasis of osteosarcoma cells by downregulation of long non-coding RNA colon cancer-associated transcript 2 targeting microRNA-143.

Bi Fengjiang F Chen Can C Fu Jing J Yu Lei L Geng Jia J

Oncology letters 20210208 4

Osteosarcoma is a malignant bone tumor, which has a high incidence in children and adolescents. However, the pathogenesis of osteosarcoma remains unclear. Long noncoding RNA (lncRNA) is a new potential therapeutic target and diagnostic biomarker for osteosarcoma. Hence, the present study aimed to explore the effect of lncRNA colon cancer-associated transcript (CCAT2) on osteosarcoma and its potential underlying mechanisms. For this purpose, the proliferation of osteosarcoma cells was measured us ...[more]

PMID: 33664828

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Project description:BackgroundTo investigate the role of microRNA-376b-3p (miR-376b-3p) and regulator of G protein signaling 1 (RGS1) in the proliferation, metastasis, and apoptosis of osteosarcoma.MethodsDifferentially expressed genes (DEGs) between tumor and normal tissues from GSE14359 and GSE33382 in the cancer genome atlas (TCGA) dataset were analyzed with GEO2R online. Similarly, differentially expressed miRNAs from GSE70367 were also analyzed with GEO2R. The interaction between the differentially expressed miRNAs and the shared distal metastasis-related DEGs from the two datasets were analyzed using miRWalk and Cytoscape. RGS1 and miR-376-3p were chosen to verify the prediction. RGS1 stably expressing and silencing cells were established based on the MG63 and U2OS cell lines. The targeting of RGS1 with miR-376b-3p was confirmed with Starbase prediction and luciferase reporter assay. Cell proliferation, metastasis, and apoptosis were characterized in vitro and in xenograft mice.ResultsA total of 10 up-regulated and 8 down-regulated DEGs were characterized as shared metastasis-related DEGs for GSE14359 and GSE33382. Among these DEGs, RGS1 was targeted with miR-376b-3p, a predicted down-regulated miRNA in GSE70367. High expression of RGS1 predicted proliferation, invasion, metastases, and poor prognosis in osteosarcoma. Overexpression of RGS1 promoted proliferation, invasion, mobility, and stemness in MG63 and U2OS cells, while silencing of RGS1 had the opposite effect in both cell lines. High expression of RGS1 promoted tumor growth in xenograft nude mice. RGS1 was targeted with miR-376b-3p; the addition of miR-376b-3p down-regulated RGS1, and suppressed cell proliferation, invasion, and metastasis. Meanwhile, sponging of miR-376b-3p had the opposite effect. The suppressive effects of miR-376b-3p could be abolished with RGS1, as cell proliferation, stemness, metastasis, and invasion were all promoted with RGS1 co-transfection in both cell lines.ConclusionsOur study indicated that RGS1 is a tumor-promoting gene in osteosarcoma, which could be inhibited with miR-376b-3p.

Dataset Information

Inhibiting proliferation and metastasis of osteosarcoma cells by downregulation of long non-coding RNA colon cancer-associated transcript 2 targeting microRNA-143.

Publications

Inhibiting proliferation and metastasis of osteosarcoma cells by downregulation of long non-coding RNA colon cancer-associated transcript 2 targeting microRNA-143.

Similar Datasets

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