Zhang Qi, Li Qiang, Xu Tao, Jiang Hui, Xu Lin-Gen
Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.
Oncol Rep. 2016 Jun;35(6):3541-7. doi: 10.3892/or.2016.4713. Epub 2016 Mar 29.
MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.
微小RNA（miRNA）在鼻咽癌（NPC）的进展中起关键作用，鼻咽癌是一种高度侵袭性和转移性癌症，在中国南方广泛流行。miR-491-5p与多种类型的癌症有关；然而，其在鼻咽癌中的生物学作用和潜在机制尚未得到充分探索。在本研究中，我们发现与相应的正常组织和细胞系相比，miR-491-5p在鼻咽癌组织和细胞系中表达下调。miR-491-5p的过表达显著抑制体外细胞增殖、迁移和侵袭，并抑制体内肿瘤生长。使用miRNA靶标预测算法和报告基因检测，我们表明miR-491-5p通过直接靶向Notch3 mRNA的3'非翻译区（3'-UTR）在mRNA和蛋白质水平上抑制Notch3表达。Notch3的过表达显著逆转了miR-491-5p的肿瘤抑制作用。综上所述，本研究揭示了miR-491-5p与Notch3在鼻咽癌发病机制中的机制联系，并且miR-491-5p具有作为鼻咽癌治疗靶点的潜力。
