Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, China; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
Exp Cell Res. 2022 Sep 1;418(1):113244. doi: 10.1016/j.yexcr.2022.113244. Epub 2022 Jun 10.
PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC. In HCC cells, overexpressing PLIN2 promoted cell proliferation, PLIN2-deficiency inhibited cell vitality. Mechanistically, silencing of PLIN2 expression downregulated hypoxia inducible factor 1-α (HIF1α) expression and this downregulation in turn inhibited the targeting genes of HIF1α. Furthermore, we found that PLIN2 stabilized and retarded the degradation of the HIF1α through autophagy-lysosomal pathway by inhibiting AMPK/ULK1. Collectively, we clarified the carcinogenic role of PLIN2 in HCC and suggested a prognostic biomarker for diagnosis and clinical therapy in the future.
PLIN2 在几种人类恶性肿瘤中失调，影响癌症进展。然而，PLIN2 在调节肝细胞癌 (HCC) 进展中的作用尚不清楚。在这里，我们揭示了 PLIN2 在 HCC 细胞和组织中频繁上调，并且增加的 PLIN2 表达与 HCC 的预后不良结果相关。在 HCC 细胞中，过表达 PLIN2 促进细胞增殖，PLIN2 缺陷抑制细胞活力。在机制上，沉默 PLIN2 的表达下调了缺氧诱导因子 1-α (HIF1α) 的表达，而这种下调反过来又抑制了 HIF1α 的靶向基因。此外，我们发现 PLIN2 通过抑制 AMPK/ULK1 稳定和延迟 HIF1α 通过自噬-溶酶体途径的降解。总之，我们阐明了 PLIN2 在 HCC 中的致癌作用，并为未来的诊断和临床治疗提供了一个预后生物标志物。
