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长链非编码 RNA NBR2 通过调控自噬抑制肝癌细胞的发生。

LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma.

机构信息

Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China.

出版信息

Biomed Pharmacother. 2021 Jan;133:111023. doi: 10.1016/j.biopha.2020.111023. Epub 2020 Dec 1.

Abstract

Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.

摘要

长链非编码 RNA(lncRNAs)已被证实其在肿瘤发生中发挥着越来越重要的作用,它们可能成为癌症治疗的新型生物标志物。lncRNA NBR2(BRCA1 基因 2 的邻居)是一种新发现的 lncRNA,在几种癌症中表达降低。然而,lncRNA NBR2 是否参与肝癌和自噬仍然未知。我们发现,在晚期患者中,NBR2 表达较低的 HCC 病例的总生存率明显低于 NBR2 表达较高的病例。而且,NBR2 的表达与 HCC 细胞系的恶性程度和肝癌的分化呈负相关。此外,NBR2 抑制肝癌细胞的增殖、侵袭和迁移。我们进一步发现,NBR2 通过 ERK 和 JNK 通路抑制细胞保护性自噬来抑制 HCC 细胞增殖。此外,NBR2 通过 ERK 和 JNK 通路抑制 Beclin 1 依赖性自噬。总之,NBR2 通过 ERK 和 JNK 通路至少部分抑制自噬诱导的细胞增殖。这些数据表明,NBR2 在肝癌中作为一种肿瘤抑制基因发挥作用。本研究为肝癌提供了新的见解和治疗策略。

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