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Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.

Xiao S, Chang RM, Yang MY, Lei X, Liu X, Gao WB, Xiao JL, Yang LY - Hepatology (2016)

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.

View Article: PubMed Central - PubMed

Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.

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Related in: MedlinePlus

ACTL6A activates Notch signaling by SOX2. (A) mRNA and protein expressions of ACTL6A, SOX2, and key members of Notch1 signaling were detected in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells. (B) mRNA and protein expressions of ACTL6A, SOX2, Notch1, and Hes1 in ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (C) The cytoskeleton, migration, invasion, and EMT marker expression assays of ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (D) Representative triple IF images showed that ACTL6A, SOX2, and NICD1 were colocalized in HCC tissue detected by confocal laser scanning microscope (yellow arrows indicate colocalization cells). (E) The schematic diagram of ACTL6A activating Notch1 signaling by SOX2, and promoting metastasis and EMT of HCC. Abbreviation: DAPI, 4′,6‐diamidino‐2‐phenylindole.
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hep28417-fig-0006: ACTL6A activates Notch signaling by SOX2. (A) mRNA and protein expressions of ACTL6A, SOX2, and key members of Notch1 signaling were detected in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells. (B) mRNA and protein expressions of ACTL6A, SOX2, Notch1, and Hes1 in ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (C) The cytoskeleton, migration, invasion, and EMT marker expression assays of ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (D) Representative triple IF images showed that ACTL6A, SOX2, and NICD1 were colocalized in HCC tissue detected by confocal laser scanning microscope (yellow arrows indicate colocalization cells). (E) The schematic diagram of ACTL6A activating Notch1 signaling by SOX2, and promoting metastasis and EMT of HCC. Abbreviation: DAPI, 4′,6‐diamidino‐2‐phenylindole.

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).


Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.

Xiao S, Chang RM, Yang MY, Lei X, Liu X, Gao WB, Xiao JL, Yang LY - Hepatology (2016)

ACTL6A activates Notch signaling by SOX2. (A) mRNA and protein expressions of ACTL6A, SOX2, and key members of Notch1 signaling were detected in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells. (B) mRNA and protein expressions of ACTL6A, SOX2, Notch1, and Hes1 in ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (C) The cytoskeleton, migration, invasion, and EMT marker expression assays of ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (D) Representative triple IF images showed that ACTL6A, SOX2, and NICD1 were colocalized in HCC tissue detected by confocal laser scanning microscope (yellow arrows indicate colocalization cells). (E) The schematic diagram of ACTL6A activating Notch1 signaling by SOX2, and promoting metastasis and EMT of HCC. Abbreviation: DAPI, 4′,6‐diamidino‐2‐phenylindole.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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hep28417-fig-0006: ACTL6A activates Notch signaling by SOX2. (A) mRNA and protein expressions of ACTL6A, SOX2, and key members of Notch1 signaling were detected in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells. (B) mRNA and protein expressions of ACTL6A, SOX2, Notch1, and Hes1 in ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (C) The cytoskeleton, migration, invasion, and EMT marker expression assays of ACTL6A‐interfered HCC cells with SOX2 knockdown or ectopic expression. (D) Representative triple IF images showed that ACTL6A, SOX2, and NICD1 were colocalized in HCC tissue detected by confocal laser scanning microscope (yellow arrows indicate colocalization cells). (E) The schematic diagram of ACTL6A activating Notch1 signaling by SOX2, and promoting metastasis and EMT of HCC. Abbreviation: DAPI, 4′,6‐diamidino‐2‐phenylindole.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.

Show MeSH
Related in: MedlinePlus