Abstract：Actin-like 6A (ACTL6A), also known as BAF53A, is an SWI/SNF subunit of chromatin-remodeling factors and plays an important role in regulating stem cell function. Recent studies found that ACTL6A was involved in tumor occurrence and development. However, the mechanism of ACTL6A in cisplatin resistance is still unclear. This study investigated the biological function and molecular mechanism of ACTL6A in maintaining cancer stem cell function and cisplatin resistance. First, analysis from TCGA, GEO, and GEPIA databases showed that ACTL6A expression levels in lung adenocarcinoma (LUAD) tissues and cisplatin resistant cells were dramatically higher than that in adjacent normal tissues and cisplatin sensitive cells (P＜0.05), and ACTL6A high expression was positively associated with a poor prognosis of LUAD. Knockdown of ACTL6A enhanced cisplatin sensitivity (P＜0.05), reduced tumor sphere (P＜0.05), inhibited cell migration (P＜0.05), and promoted cell apoptosis (P＜0.05) in A549 cells. Western blotting showed that knockdown of ACTL6A increased the protein expression of E-cadherin, and decreased the protein expression of N-cadherin, vimentin, and twist. Moreover, knockdown of ACTL6A inhibited the expression of cancer stem cell markers, including ALDH3A1, ALDH4A1, SOX2, OCT4, and Nanog. Subsequently, Hippo/YAP signaling-related proteins were analyzed by Western blotting. The results showed the expression of beta-TRCP and YAP was decreased in A549 cell with knockdown of ACTL6A. However, phosphorylation levels at S127 and S397 of YAP were increased and inhibited translocation of YAP into the nucleus for regulating related gene expression. In summary, ACTL6A maintained the stemness of lung cancer stem cells and promoted cisplatin resistance in A549 cells by inhibiting activation of the Hippo signaling pathway.
唐艳, 谢学琴, 黄玖红, 杨东林, 胡春生. 肌动蛋白样6A抑制Hippo/YAP信号通路促进肺腺癌细胞对顺铂的耐受[J]. 中国生物化学与分子生物学报, 2021, 37(10): 1336-1344.
TANG Yan, XIE Xue-Qin, HUANG Jiu-Hong, YANG Dong-Lin, HU Chun-Sheng. ACTL6A Induces Cisplatin Resistance in the Lung Adenocarcinoma by Inhibiting the Hippo/YAP Signaling Pathway. Chinese Journal of Biochemistry and Molecular Biol, 2021, 37(10): 1336-1344.
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