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: To study expression of ACTL6A in HCC cells and tissues, real‐time polymerase chain reaction (PCR), reverse‐transcription PCR (RT‐PCR), and western blotting were performed. Compared with L02 cells, which are immortalized human normal liver cells, ACTL6A messenger RNA (mRNA) and protein were highly expressed in HCC cells (Fig. 1A). Then, expression of ACTL6A in HCCs and their corresponding ANLTs were also detected. Thirty pairs of HCCs (SHCC [single nodule <5 cm] = 10; SLHCC = 10; NHCC = 10) and corresponding ANLTs were used here and compared with normal liver tissue from a hepatic hemangioma patient (L495). Consistent with the increased ACTL6A expression in HCC cell lines, ACTL6A expression in HCC tissues was markedly higher than ANLTs and normal liver tissue (Fig. 1B). ACTL6A expression in HCC was analyzed by immunohistochemistry (IHC), which suggested that ACTL6A protein was highly expressed in HCC (Fig. 1C). Comparing samples with metastasis to nonmetastasis samples and ANLTs, metastasis samples have the highest intensities of ACTL6A staining, whereas ANLTs have the lowest intensities (Supporting Fig. 2A). Notably, ACTL6A expression in high‐metastasis potential cell lines, such as HCCLM3, MHCC97‐H, and Hep3B was higher than in low‐metastasis potential cell lines PLC/PRF5, SMMC7721, and HepG2 (Fig. 1A,B). ACTL6A expression in SHCC, SLHCC, and NHCC was also step‐increased (Supporting Fig. 2B). These data indicated that ACTL6A was up‐regulated in HCCs and it might be correlated with HCC invasion and metastasis.
Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.