Division of Gastroenterology and Hepatology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, Zhejiang, 315000, China.
Hongkou Branch of Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
World J Surg Oncol. 2020 May 30;18(1):113. doi: 10.1186/s12957-020-01884-x.
Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms.
The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection.
HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition.
HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.
肝癌（HCC）的发病率和死亡率都很高，因此仍然是中国的一个主要健康负担。长链非编码 RNA（lncRNA）在肿瘤进展中发挥着重要作用，为 HCC 的诊断和预后预测或治疗提供了新的途径。本研究旨在探讨 HIF1A-AS1 在 HCC 进展过程中的作用及其相关机制。
通过实时定量 PCR 检测 50 对癌组织和相邻正常组织中 HIF1A-AS1 的表达。用营养缺乏培养基诱导 HCC 细胞凋亡，用细胞计数试剂盒-8 和流式细胞仪检测。用小干扰 RNA 转染抑制 HCC 细胞中的 HIF1A-AS1。
HIF1A-AS1 在 HCC 组织中高表达，与肿瘤大小、TNM 分期和淋巴结转移有关。与低 HIF1A-AS1 组相比，高 HIF1A-AS1 组的总生存期和无病生存期更短。在正常培养条件下，HIF1A-AS1 在 HCC 细胞系（7721 和 Huh7）中的表达明显高于正常肝细胞系 L02。然而，在营养缺乏条件下，HIF1A-AS1 在 HCC 和正常肝细胞系中的表达均明显增加，并随无营养培养时间的延长而增加。抑制 HIF1A-AS1 可促进饥饿诱导的 HCC 细胞凋亡。此外，抑制 HIF1A-AS1 还可以减少饥饿诱导的 HCC 细胞自噬。抑制 HIF1A-AS1 后，HCC 细胞中 HIF-1α 和磷酸化 mTOR 的表达明显降低。
HIF1A-AS1 在 HCC 中高表达，并与 HCC 预后相关，可通过减少 HIF-1α/mTOR 介导的自噬来调节饥饿诱导的 HCC 细胞凋亡，促进 HCC 细胞的进展。
