Yue Lei, Guo Jing
Department of Emergency, The Central Hospital of Luoyang, Luoyang, Henan, China.
Department of Laboratory, Xi'an Central Hospital, Xi'an, Shaanxi, China.
J Cell Physiol. 2019 Sep;234(9):15911-15921. doi: 10.1002/jcp.28248. Epub 2019 Feb 4.
Pancreatic carcinoma is one of the most common and lethal human malignancies worldwide. Long noncoding RNAs (lncRNAs) are a well-known type of nonprotein-coding transcripts implicated in cancer development and progression. Increasing evidence has indicated that lncRNA tumor suppressor candidate 7 (TUSC7) is a novel cancer suppressor gene in various cancers. Nevertheless, the function of TUSC7 in pancreatic carcinoma is urgent to be clarified. We found that TUSC7 was notably decreased in tissues and cell lines of pancreatic carcinoma. Moreover, the low expression of TUSC7 was correlated with advanced clinical grades and poorer overall survival. Our findings revealed that TUSC7 repressed cell proliferation, migration, invasion, epithelial-mesenchymal transition, and stemness whereas facilitated cell apoptosis of pancreatic carcinoma cells. Further investigations demonstrated that miR-371a-5p directly bound with TUSC7 and negatively regulated by TUSC7. MiR-371a-5p rescued the inhibitory effects of TUSC7 on the development of pancreatic carcinoma. We conclude that lncRNA TUSC7 suppresses pancreatic carcinoma progression by modulating miR-371a-5p expression, indicating an innovative therapeutic strategy for pancreatic carcinoma.
胰腺癌是全球最常见且致命的人类恶性肿瘤之一。长链非编码RNA（lncRNAs）是一类众所周知的非蛋白质编码转录本，与癌症的发生和发展有关。越来越多的证据表明，lncRNA肿瘤抑制候选基因7（TUSC7）是多种癌症中的一种新型抑癌基因。然而，TUSC7在胰腺癌中的功能亟待阐明。我们发现，TUSC7在胰腺癌组织和细胞系中显著降低。此外，TUSC7的低表达与临床晚期分级及较差的总生存期相关。我们的研究结果表明，TUSC7抑制胰腺癌细胞的增殖、迁移、侵袭、上皮-间质转化和干性，同时促进细胞凋亡。进一步研究表明，miR-371a-5p直接与TUSC7结合，并受TUSC7负调控。miR-371a-5p可挽救TUSC7对胰腺癌发展的抑制作用。我们得出结论，lncRNA TUSC7通过调节miR-371a-5p的表达来抑制胰腺癌进展，这为胰腺癌提供了一种创新的治疗策略。
