Long non-coding RNA SNHG1 activates glycolysis to promote hepatocellular cancer progression through the miR-326/PKM2 axis
Long non-coding RNA SNHG1 activates glycolysis to promote hepatocellular cancer progression through the miR-326/PKM2 axis
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DOI：
10.1002/jgm.3440
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发表时间：
2022-07-25
影响因子：
3.5
通讯作者：
Yang, Qing
中科院分区：
文献类型：
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作者：
Wang, Yue;Yang, Fan;Yang, Qing
背景肝细胞癌（Hepatocellular cancer，HCC）是一种预后极差的恶性肿瘤.在本研究中，我们的目的是研究SNHG 1在肝癌进展中的作用和潜在机制。方法结合生物信息学和实验验证，探讨SNHG 1在肝癌中的临床意义。采用Cell Counting Kit-8细胞计数法、细胞集落形成实验和裸鼠皮下成瘤实验评价SNHG 1的促增殖能力。测定葡萄糖消耗和乳酸产生，以探讨SNHG 1在糖酵解中的调节作用。通过核质分离、实时定量聚合酶链反应和Western blot、染色质免疫沉淀、荧光素酶报告基因和RNA免疫沉淀等方法研究SNHG 1在HCC中的分子机制。结果SNHG 1在HCC中的表达明显增高，且与预后不良呈正相关。E2 F1与SNHG 1启动子区结合以激活SNHG 1转录。此外，SNHG 1作为miR-326的分子海绵，隔离miR-326与丙酮酸激酶M2（PKM 2）的相互作用，促进PKM 2的表达。激活PKM 2表达是SNHG 1促进糖酵解和肝癌细胞增殖的机制之一。结论E2 F1激活的SNHG 1通过调节miR-326/PKM 2轴促进HCC细胞糖酵解和增殖。靶向SNHG 1可能是HCC的一种有前途的治疗选择。
Background Hepatocellular cancer (HCC) is a lethal malignancy with extremely poor prognosis. In the present study, we aimed to investigate the role and underlying mechanism of SNHG1 in HCC progression. Methods Combined with bioinformatics and experimental validation, we explored the clinical significance of SNHG1 in HCC. A Cell Counting Kit-8 assay, cell colony formation assay, and subcutaneous tumorigenesis experiments of nude mice were conducted to evaluate the pro-proliferative capacity of SNHG1. Glucose consumption and lactate production were measured to explore the regulatory role of SNHG1 in glycolysis. Nuclear-cytoplasmic separation, quantitative real-time polymerase chain reaction and Western blot assays, chromatin immunoprecipitation, and luciferase reporter and RNA immunoprecipitation assays were performed to investigate the molecular mechanisms of SNHG1 in HCC. Results SNHG1 expression was dramatically increased in HCC and positively correlated with poor prognosis. E2F1 bound to the SNHG1 promoter region to activate SNHG1 transcription. Furthermore, SNHG1 served as a molecular sponge for miR-326 to sequester the interaction of miR-326 and pyruvate kinase M2 (PKM2), facilitating the expression of PKM2. Activating PKM2 expression was revealed to be one of mechanisms of SNHG1 with respect to promoting glycolysis and the proliferation of HCC cells. Conclusions E2F1-activated SNHG1 modulates the miR-326/PKM2 axis to facilitate glycolysis and the proliferation of HCC cells. Targeting SNHG1 could be a promising therapeutic option for HCC.