Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Aging (Albany NY). 2020 Mar 11;12(5):4527-4546. doi: 10.18632/aging.102907.
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and currently the second leading cause of cancer-related mortality worldwide. One recent study reported that lncRNA-LALR1 promotes liver regeneration, the role and underlying mechanisms of lncRNA-LALR1 in HCC remain largely unknown. In this study, we demonstrated that lncRNA-LALR1 was significantly upregulated in HCC tissues compared with adjacent tissues and high expression of lncRNA-LALR1 was associated with advanced TNM stage, poor differentiation, and distant metastasis. RNA Fluorescence in situ hybridization analysis showed lncRNA-LALR1 was expressed not only in cytoplasm but also in nucleolus. Knockdown of lncRNA-LALR1 obviously inhibited HCC cells growth and invasion and . Besides, transcriptomic analysis and subsequent confirmation revealed that lncRNA-LALR1 upregulated small nucleolar RNA SNORD72 via binding with SNORD72 and stabilized ID2 mRNA. SNORD72 was overexpressed in HCC tissues and enhanced HCC cells proliferation, colony formation and invasion. Overexpression of SNORD72 could also stabilize ID2 mRNA and rescue the inhibitory effect of silencing lncRNA-LALR1. In conclusion, lncRNA-LALR1 is highly expressed in HCC and promotes tumor growth and invasion by upregulating SNORD72 to stabilize ID2 mRNA, implying that lncRNA-LALR1 might be a novel target for intervention of HCC.
肝细胞癌 (HCC) 是最常见的癌症之一,目前是全球癌症相关死亡的第二大主要原因。最近的一项研究表明,长链非编码 RNA-LALR1 促进肝脏再生,lncRNA-LALR1 在 HCC 中的作用和潜在机制在很大程度上尚不清楚。在这项研究中,我们证明与相邻组织相比,lncRNA-LALR1 在 HCC 组织中明显上调,lncRNA-LALR1 的高表达与晚期 TNM 分期、低分化和远处转移有关。RNA 荧光原位杂交分析表明 lncRNA-LALR1 不仅在细胞质中表达,而且在核仁中表达。lncRNA-LALR1 的敲低明显抑制 HCC 细胞的生长和侵袭,并且转录组分析和随后的验证表明,lncRNA-LALR1 通过与 SNORD72 结合而上调小核仁 RNA SNORD72,并稳定 ID2 mRNA。SNORD72 在 HCC 组织中过度表达,并增强 HCC 细胞的增殖、集落形成和侵袭。SNORD72 的过表达也可以稳定 ID2 mRNA,并挽救沉默 lncRNA-LALR1 的抑制作用。总之,lncRNA-LALR1 在 HCC 中高表达,并通过上调 SNORD72 稳定 ID2 mRNA 促进肿瘤生长和侵袭,表明 lncRNA-LALR1 可能是 HCC 干预的一个新靶点。