ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.

中文翻译：

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ATG4D 的沉默通过 Akt/Caspase-3 通路抑制肝细胞癌的增殖并增强顺铂诱导的细胞凋亡。

ATG4D 是自噬相关蛋白 4 (ATG4) 家族的成员，在癌症的自噬和细胞凋亡之间起相互作用。然而，尚未确定 ATG4D 在肝细胞癌 (HCC) 中的作用。在此，本研究旨在探讨ATG4D在调节HCC细胞凋亡中的作用及其潜在机制。ATG4D 在 MHCC-97L HCC 细胞中被沉默，然后检测细胞增殖和凋亡。与配对的非肿瘤组织相比，HCC 组织中 ATG4D 的表达显着上调。体外试验表明，ATG4D 的沉默显着抑制了 MHCC-97L 细胞的细胞增殖，促进了细胞凋亡，并增强了对顺铂的敏感性。此外，ATG4D 的沉默降低了 Akt 的磷酸化并增加了 caspase-3 的蛋白质水平。综合起来，ATG4D 可能在 HCC 进展中发挥致癌作用。这些发现表明 ATG4D 可作为 HCC 治疗的治疗靶点。