肝癌是导致全球癌症相关死亡的主要原因之一。自噬在肝癌的发生发展中至关重要，但是涉及到自噬诱导的肝癌恶性发展的关键分子调控机制尚不明确。前期通过高通量数据库TCGA分析，我们发现KCNK9蛋白在肝癌中的表达显著上升，并且与肝癌患者较差的生存预后密切相关。预实验结果显示KCNK9可以引起自噬从而促进肝癌细胞增殖； KCNK9可通过结合AKT，抑制AKT/mTOR信号通路,上调Atg7的表达；同时我们还发现过表达KCNK9可能通过调节Beclin1，上调Atg16的表达, 促进自噬，但涉及到其中的分子调控机制还未得到充分阐明。本项目将以过表达或沉默表达KCNK9的细胞为模型，探讨KCNK9抑制AKT/mTOR信号通路和调控Beclin1的具体分子机制；并结合临床样品，验证KCNK9 促进肝癌细胞增殖的功能，为诊断和治疗肝癌提供新的分子标记物和分子靶标。

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Autophagy is vitally important in the tumorigenesis and progression of hepatocellular carcinoma, but the key molecular mechanism associated with autophagy-induced hepatocellular carcinoma is unclear. Previously, by analyzing datasets from The Cancer Genome Atlas (TCGA), we found that KCNK9 was markedly upregulated in hepatocellular carcinoma and higher expression of KCNK9 significantly correlated with poorer overall survival and relapse-free survival of hepatocellular carcinoma patients. Furthermore, our preliminary data demonstrated that overexpression of KCNK9 promoted the proliferation of hepatocellular carcinoma by inducing autophagy. Moreover, KCNK9 could bind to AKT, inhibit AKT/mTOR signaling pathway AND subsequently upregulate expression of Atg7. Meanwhile, we observed that KCNK9 could upregulate Atg16 via regulating Beclin 1. Taken together, these results indicated that KCNK9 plays an important role in promoting proliferation of hepatocellular carcinoma. However, the mechanisms of how KCNK9 inhibit NF-κB signaling pathway and regulate Beclin1 in HCC remain largely elusive. Therefore, in the present project, we aim to further investigate the mechanism by which KCNK9 promotes the proliferation of hepatocellular carcinoma, which may provide theoretical basis for identifying new biomarkers and targets for the diagnosis and treatment of hepatocellular carcinoma.