Background: LncRNA TMC3-AS1 expression is affected by lipopolysaccharide (LPS), a contributor to osteoporosis (OS). Therefore, we hypothesized that TMC3-AS1 could inhibit osteoblast apoptosis and interact with miR-708, a regulator of osteoblast apoptosis in OS.
Methods: Differential expression of TMC3-AS1 and miR-708 (mature and premature) in OS patients and controls was analyzed using RT-qPCR. Subcellular location of TMC3-AS1 in osteoblasts was analyzed using subcellular fractionation assay. The direct interaction between TMC3-AS1 and premature miR-708 was analyzed using RNA pulldown assay. The role of TMC3-AS1 and miR-708 in the expression of each other was explored with overexpression assays. Cell apoptosis induced by LPS was analyzed using cell apoptosis assay.
Results: TMC3-AS1 and premature miR-708 were highly expressed in OS and were upregulated by LPS in osteoblasts. In contrast, mature miR-708 was under-expressed in OS and downregulated by LPS. TMC3-AS1 directly interacted with premature miR-708 and was detected in both the nuclear and cytoplasm fractions. TMC3-AS1 decreased premature miR-708 level and increased mature miR-708 level. Moreover, TMC3-AS1 increased LPS-induced cell apoptosis and suppressed the role of miR-708 in cell apoptosis.
Conclusion: TMC3-AS1 is highly expressed in OS and promotes LPS-induced osteoblast apoptosis by reducing miR-708 maturation.
Keywords: osteoporosis, TMC3-AS1, miR-708, osteoblast