SND1 acts as an anti-apoptotic factor via regulating the expression of lncRNA <i>UCA1</i> in hepatocellular carcinoma

Multifunctional SND1 (staphylococcal nuclease and tudor domain containing 1) protein is reportedly associated with different types of RNA molecules, including mRNA, miRNA, pre-miRNA, and dsRNA. SND1 has been implicated in a number of biological processes in eukaryotic cells, including cell cycle, DNA damage repair, proliferation, and apoptosis. However, the specific molecular mechanism regarding the anti-apoptotic role of SND1 in mammalian cells remains largely elusive. In this study, the analysis of the online HPA (human protein atlas) and TCGA (the cancer genome atlas) databases showed the significantly high expression of SND1 in liver cancer patients. We found that the downregulation or complete depletion of SND1 enhanced the apoptosis levels of HepG2 and SMMC-7721 cells upon stimulation with 5-Fu (5-fluorouracil), a chemotherapeutic drug for HCC (hepatocellular carcinoma). SND1 affected the 5-Fu-induced apoptosis levels of HCC cells by modulating the expression of <i>UCA1</i> (urothelial cancer associated 1), which is a lncRNA (long non-coding RNA). Moreover, MYB (MYB proto-oncogene, transcription factor) may be involved in the regulation of SND1 in <i>UCA1</i> expression. In summary, our study identified SND1 as an anti-apoptotic factor in hepatocellular carcinoma cells via the modulation of lncRNA <i>UCA1</i>, which sheds new light on the relationship between SND1 protein and lncRNA.多功能SND1（葡萄球菌核酸酶及tudor结构域包含蛋白1，staphylococcal nuclease and tudor domain containing 1）蛋白据报道可与多种RNA分子结合，涵盖信使RNA（mRNA）、微小RNA（miRNA）、前体微小RNA（pre-miRNA）及双链RNA（dsRNA）。SND1已被证实参与真核细胞的诸多生物学过程，包括细胞周期调控、DNA损伤修复、细胞增殖与细胞凋亡。然而，SND1在哺乳动物细胞中发挥抗凋亡作用的具体分子机制仍尚未完全阐明。本研究通过对在线人类蛋白质组图谱（HPA，human protein atlas）与癌症基因组图谱（TCGA，the cancer genome atlas）数据库开展分析，发现SND1在肝癌患者体内呈现显著高表达。我们发现，下调或完全敲除SND1可提升HepG2与SMMC-7721细胞在经用于肝细胞癌（HCC）的化疗药物5-氟尿嘧啶（5-Fu，5-fluorouracil）刺激后的凋亡水平。SND1可通过调控长链非编码RNA（lncRNA，long non-coding RNA）*UCA1*（尿路上皮癌相关基因1，urothelial cancer associated 1）的表达，影响5-氟尿嘧啶诱导的肝癌细胞凋亡水平。此外，MYB（MYB原癌基因，转录因子，MYB proto-oncogene, transcription factor）可能参与SND1对*UCA1*表达的调控过程。综上，本研究证实SND1通过调控长链非编码RNA *UCA1*，成为肝癌细胞中的抗凋亡因子，该发现为阐明SND1蛋白与长链非编码RNA之间的相互关系提供了全新视角。