EF‐24 inhibits TPA‐induced cellular migration and MMP‐9 expression through the p38 signaling pathway in cervical cancer cells

Abstract

Diphenyl difluoroketone (EF-24), a synthetic curcumin analog, has enhanced bioavailability over curcumin. EF-24 acts more powerful bioactivity for anti-inflammatory and anti-cancer activity. However, the effects and mechanism of EF-24 on cervical cancer has not been fully investigated. Herein, this study evaluated the effects of EF-24 on TPA-induced cellular migration of cervical cancer. The results showed that EF-24 substantially reduced the cellular migration and cellular invasion of the HeLa and SiHa cells. Moreover, gelatin zymography, western blotting analyses and real-time PCR revealed that EF-24 suppressed Matrix metalloproteinase-9 (MMP-9) activity, protein expression and mRNA levels. Mechanistically, EF-24 inhibited the phosphorylation of the p38 signaling pathway. In conclusion, EF-24 inhibited TPA-induced cellular migration and cellular invasion of cervical cancer cell lines through modulating MMP-9 expression via downregulating signaling p38 pathway and EF-24 may have potential to serve as a chemopreventive agent of cervical cancer.

RBM15 m6A modification‐mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling

“…In this work, we intended to characterize OTUB2 expression and function in CC and explore its relation to RBM15 and AKT/mTOR signaling pathway. Our findings showed that RBM15-mediated m 6 A modification led to OTUB2 upregulation in CC cells, thereby promoting malignant phenotypes of CC cells via activation of the AKT/mTOR signaling. Taken together, this study uncovered a novel regulatory molecular mechanism of OTUB2 in CC in vitro, providing the potential of OTUB2 as a therapeutic target for CC.…”

“…N6-methyladenosine (m 6 A) modification of messenger RNAs (mRNAs) is highly conserved in mammals 19 and has huge impacts on gene regulation. 20 Recent studies have demonstrated the important role of m 6 A RNA methylation in human cancers, including CC. 21 The m 6 A methylation is a reversible process involving RNA methyltransferases ("writers"), RNA demethylases ("erasers"), and RNA-binding proteins ("readers").…”

“…20 Recent studies have demonstrated the important role of m 6 A RNA methylation in human cancers, including CC. 21 The m 6 A methylation is a reversible process involving RNA methyltransferases ("writers"), RNA demethylases ("erasers"), and RNA-binding proteins ("readers"). 22 As an m 6 A writer, RNA binding motif protein 15 (RBM15) can bind to RNA through spliceosomes, thereby regulating RNA splicing, translation, and stability.…”

“…21 The m 6 A methylation is a reversible process involving RNA methyltransferases ("writers"), RNA demethylases ("erasers"), and RNA-binding proteins ("readers"). 22 As an m 6 A writer, RNA binding motif protein 15 (RBM15) can bind to RNA through spliceosomes, thereby regulating RNA splicing, translation, and stability. 23 RBM15 has been demonstrated to exert carcinogenic effects in human cancers by regulating mRNA stability and expression in an m 6 A-dependent manner.…”

“…22 As an m 6 A writer, RNA binding motif protein 15 (RBM15) can bind to RNA through spliceosomes, thereby regulating RNA splicing, translation, and stability. 23 RBM15 has been demonstrated to exert carcinogenic effects in human cancers by regulating mRNA stability and expression in an m 6 A-dependent manner. 24 Furthermore, there is convincing evidence that RBM15 contributes to the malignant development of CC and possesses certain prognostic values.…”