Dataset Information

LncRNA OR3A4 Regulated the Growth of Osteosarcoma Cells by Modulating the miR-1207-5p/G6PD Signaling.

ABSTRACT: Background:Increasing evidence has demonstrated the importance of non-coding RNAs including long non-coding RNA (lncRNA) and microRNAs (miRNAs) in the tumorigenesis of osteosarcoma (OS). Abnormal expression of lncRNA olfactory receptor family 3 subfamily A member 4 (OR3A4) was found in multiple human cancers; however, the function of OR3A4 in OS remains largely unknown. Materials and Methods:The expression level of OR3A4 in OS tissues and cell lines was detected by RT-qPCR. Cell counting kit-8 assay, colony formation and flow cytometry analysis were performed to determine the growth of OS cells. The targets of OR3A4 were predicted using the miRDB database. The binding between OR3A4 and miRNAs was confirmed by dual-luciferase reporter assay. Results:OR3A4 was overexpressed in OS tissues and correlated with the advanced progression of OS patients. Down-regulation of OR3A4 significantly inhibited the proliferation and colony formation of OS cells. Mechanistically, OR3A4 acted as a sponge of miR-1207-5p. Glucose-6-phosphate dehydrogenase (G6PD) was identified as a target of miR-1207-5p. Knockdown of OR3A4 increased the expression of miR-1207-5p and consequently, suppressed the level of G6PD in OS cells. Due to the essential role of G6PD in the pentose phosphate pathway (PPP), depletion of OR3A4 inhibited NADPH production, glucose consumption and lactate generation. Decreased level of NADPH by depletion of OR3A4 up-regulated the redox state (ROS) content and resulted in endoplasmic reticulum (ER) stress in OS cells. Restoration of G6PD significantly attenuated the cell growth inhibition induced by OR3A4 knockdown. Conclusion:Our finding suggested the critical role of OR3A4 in the proliferation of OS cells via targeting the miR-1207-5p/G6PD axis.

SUBMITTER: Wang X

PROVIDER: S-EPMC7167273 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LncRNA OR3A4 Regulated the Growth of Osteosarcoma Cells by Modulating the miR-1207-5p/G6PD Signaling.

Wang Xiaole X Chen Kunfeng K Zhao Zhijian Z

OncoTargets and therapy 20200415

<h4>Background</h4>Increasing evidence has demonstrated the importance of non-coding RNAs including long non-coding RNA (lncRNA) and microRNAs (miRNAs) in the tumorigenesis of osteosarcoma (OS). Abnormal expression of lncRNA olfactory receptor family 3 subfamily A member 4 (OR3A4) was found in multiple human cancers; however, the function of OR3A4 in OS remains largely unknown.<h4>Materials and methods</h4>The expression level of OR3A4 in OS tissues and cell lines was detected by RT-qPCR. Cell c ...[more]

PMID: 32346295

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Project description:The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3'-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR-372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.

Dataset Information

LncRNA OR3A4 Regulated the Growth of Osteosarcoma Cells by Modulating the miR-1207-5p/G6PD Signaling.

Publications

LncRNA OR3A4 Regulated the Growth of Osteosarcoma Cells by Modulating the miR-1207-5p/G6PD Signaling.

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