Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting Rd, Xuanwu District, Nanjing, 210000, Jiangsu Province, People's Republic of China.
J Exp Clin Cancer Res. 2017 Oct 5;36(1):138. doi: 10.1186/s13046-017-0604-3.
miR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported.
The expression level of miR-203a-3p in human NPC tissues and cell lines was detected via real-time PCR (RT-PCR). Cell proliferation, migration and invasion were assessed in vitro by MTT, colony formation and transwell assay, respectively. The function of miR-203a-3p in vivo was detected through NPC xenograft tumor growth and lung metastatic mice model. Dual-luciferase reporter assay was used to identify the direct target of miR-203a-3p.
The expression of miR-203a-3p was decreased in NPC tissues and cell lines in comparison with normal nasopharyngeal tissues and cell line. Ectopic expression of miR-203a-3p inhibited while inhibiting miR-203a-3p expression increased NPC cell proliferation, migration and invasion in vitro. MR-203a-3p overexpression suppressed xenograft tumor growth and lung metastasis in vivo. LASP1 was identified as a direct target of miR-203a-3p, which was confirmed by real-time PCR and western blotting assay. Ectopic expression of LASP1 partially reversed miR-203a-3p-mediated inhibition on proliferation, migration and invasion in NPC cells.
Collectively, miR-203a-3p suppresses tumor growth and metastasis through targeting LASP1 in NPC. The newly identified miR-203a-3p/LASP1 pathway provides further insights into the initiation and progression of NPC, which may represent a novel therapeutic target for NPC.
miR-203a-3p 被报道为一种肿瘤抑制因子,在包括鼻咽癌(NPC)在内的许多恶性肿瘤中失调。然而,其在 NPC 中的肿瘤生长和转移中的功能很少被报道。
通过实时 PCR(RT-PCR)检测人 NPC 组织和细胞系中 miR-203a-3p 的表达水平。通过 MTT、集落形成和 Transwell 测定分别在体外评估细胞增殖、迁移和侵袭。通过 NPC 异种移植肿瘤生长和肺转移小鼠模型检测 miR-203a-3p 的体内功能。双荧光素酶报告基因检测用于鉴定 miR-203a-3p 的直接靶标。
与正常鼻咽组织和细胞系相比,miR-203a-3p 在 NPC 组织和细胞系中的表达降低。miR-203a-3p 的异位表达抑制了 NPC 细胞在体外的增殖、迁移和侵袭,而抑制 miR-203a-3p 的表达则增加了 NPC 细胞的增殖、迁移和侵袭。MR-203a-3p 的过表达抑制了体内异种移植肿瘤的生长和肺转移。LASP1 被鉴定为 miR-203a-3p 的直接靶标,这通过实时 PCR 和 Western blot 分析得到了证实。LASP1 的异位表达部分逆转了 miR-203a-3p 介导的 NPC 细胞增殖、迁移和侵袭抑制作用。
总之,miR-203a-3p 通过靶向 NPC 中的 LASP1 抑制肿瘤生长和转移。新鉴定的 miR-203a-3p/LASP1 通路为 NPC 的发生和发展提供了进一步的认识,可能代表 NPC 的一种新的治疗靶点。