Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.
Bottom Line: Opposite results are observed when ACTL6A is knocked down.ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, in HCC cells.Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)-box 2 (SOX2) expression and then activate Notch1 signaling.
Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.Show MeSH
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Mentions: It has proved that ACTL6A promotes Notch signaling in HCCs; however, how ACTL6A regulates Notch1 signaling in HCC is unknown. We have reviewed literature and searched the BioGrid 3.4 database, and found that ACTL6A could interact with the SOX2 promoter.17 SOX2 is an important transcription factor that could positively transcriptional regulate Notch1, and it also could be transcriptionally regulated by Jagged123; these findings led us to hypothesize that ACTL6A could activate Notch signaling by regulating SOX2 expression. To test this, we first determined the expression levels of SOX2, Jagged1, Notch1, and Hes1 in ACTL6A‐interfered HCC cells. It showed that ectopic expression of ACTL6A could enhance SOX2, Notch1, and Hes1 expression, whereas ACTL6A knockdown markedly decreased their expression both at mRNA and protein levels. However, Jagged1 expression was not affected by ectopic expression or knockdown of ACTL6A (Fig. 6A).
Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.