Long noncoding TMPO antisense RNA 1 promotes hepatocellular carcinoma proliferation and epithelial-mesenchymal transition by targeting the microRNA-126-3p/LRP6/β-catenin axis

Long noncoding RNAs (lncRNAs) play a central role in the pathogenesis of various tumors, including hepatocellular carcinoma (HCC). TMPO antisense RNA 1 (TMPO-AS1) has been reported in many tumors. Nevertheless, the underlying mechanism whereby TMPO-AS1 influences HCC remains unclear. Our research aimed to reveal the molecular mechanism governing the function of TMPO-AS1 in HCC.

Our research demonstrated that TMPO-AS1 acts as a sponge for the tumor suppressor miR-126-3p in HCC and promotes the expression of LRP6 indirectly. Taken together, our results show that TMPO-AS1 may be regarded as a novel therapeutic target in the treatment of liver cancer.

TMPO-AS1 expression levels in HCC tissues/cells were evaluated using reverse transcriptase-polymerase chain reaction. The effect of TMPO-AS1 on the progression of HCC was observed by Cell Counting Kit-8 (CCK8), clone formation, wound healing, and transwell. The direct interaction between TMPO-AS1 and microRNA (miR)-126-3p was observed using a dual-luciferase reporter.

We found TMPO-AS1 expression to be remarkably higher in HCC specimens and associated with poor prognosis. Silencing of TMPO-AS1 not only inhibited HCC cell proliferation but also significantly reduced epithelial-to-mesenchymal transition-induced invasion and migration to a remarkable degree. According to the results from the online database analysis tools implemented to identify if TMPO-AS1 could target miR-126-3p, we found that miR-126-3p had a negative relationship with TMPO-AS1 in HCC specimens. Meanwhile, the luciferase reporter assay confirmed that TMPO-AS1 could directly act on miR-126-3p. Moreover, the silencing of miR-126-3p dramatically abolish the inhibitive influence of sh-TMPO-AS1 on HCC development. Conclusions: Our research demonstrated that TMPO-AS1 acts as a sponge for the tumor suppressor miR-126-3p in HCC and promotes the expression of LRP6 indirectly. Taken together, our results show that TMPO-AS1 may be regarded as a novel therapeutic target in the treatment of liver cancer.