Background Osteosarcoma (OS) is a highly recurrent malignancy occurring among adolescents. The goal of this research was to scrutinize the role and action mechanism of KLF3-AS1 in OS. Methods Western blotting and quantitative reverse transcription real-time PCR were conducted to ascertain the mRNA expressions of miR-338-3p, KLF3-AS1, and MEF2C in OS cell lines and tissue samples. Colony formation and CCK-8 experiments were done to evaluate the proliferative capacity of the cells. Western blotting was also executed to measure the relative expressions of the proteins Bcl-2 and Bax. RNA immunoprecipitation and dual luciferase reporter experiments were carried out to validate the target relationships among MEF2C, KLF3-AS1, and miR-338-3p. Mouse xenograft models were created to assess the influences of KLF3-AS1 on the growth of tumors in vivo. Results Elevated levels of KLF3-AS1 and MEF2C and reduced amounts of miR-338-3p were identified in OS. KLF3-AS1 targeted miR-338-3p, and miR-338-3p further targeted MEF2C. Silencing KLF3-AS1 induced apoptosis and attenuated proliferation in vitro and repressed the tumor growth in vivo. Inhibiting miR-338-3p inverted the cancer-suppressing effects of KLF3-AS1 silencing. Meanwhile, loss of MEF2C partially eliminated the effects brought about by miR-338-3p downregulation, namely the stimulation of cell growth and suppression of apoptosis. Conclusions Silencing of KLF3-AS1 could repress the growth of cells and induce apoptosis by regulating miR-338-3p/MEF2C in OS. This suggests that the regulatory axis KLF3-AS1/miR-338-3p/MEF2C is a prospective target for OS treatment.
Background Atrial fibrosis is associated with the pathogenesis of atrial fibrillation (AF). This study aims to discuss the function of circ_0079480 in atrial fibrosis and its underlying mechanism. Methods In vitro and in vivo models of atrial fibrosis were established by using angiotensin II (Ang II) to treat human atrial fibroblasts (HAFs) and C57/B6J mice. qRT-PCR and western blot were used to examine the mRNA and protein expression levels. CCK-8, EdU, cell strach, and transwell assays were performed to determine the proliferation and migration of HAFs. Dual-luciferase reporter and RIP/RNA pull-down assays were explored to identify the interaction of miR-338-3p and circ_0079480/THBS1. HE and Masson's trichrome staining experiments were performed to analyze the histopathological change in mice atrial tissues. Results Circ_0079480 expression was increased in AF patients' atrial tissues and Ang II-treated HAFs. Silencing circ_0079480 inhibited cell proliferation and migration and reduced fibrosis-associated gene expression in Ang II-treated HAFs. Circ_0079480 could target miR-338-3p to repress its expression. MiR-338-3p inhibitor blocked the inhibitory effects of circ_0079480 knockdown on HAFs proliferation, migration, and fibrosis. Thrombospondin-1 (THBS1) was confirmed as a downstream target of miR-338-3p, and circ_0079480 could sponge miR-338-3p to upregulate THBS1 expression. Moreover, silencing THBS1 suppressed Ang II-induced proliferation, migration, and fibrosis in HAFs. More importantly, depletion of circ_0079480 inactivated the THBS1/TGF-β1/Smad3 signaling by upregulating miR-338-3p. Mice experiments also confirmed the suppression of circ_0079480 knockdown on atrial fibrosis. Conclusion Circ_0079480 acts as a sponge of miR-338-3p to upregulate THBS1 expression and activate the TGF-β1/Smad3 signaling, finally promoting Ang II-induced atrial fibrosis.
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