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

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.