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微小RNA-409-3p通过靶向……抑制舌鳞状细胞癌的增殖、侵袭和迁移。

miR-409-3p suppresses the proliferation, invasion and migration of tongue squamous cell carcinoma via targeting .

作者信息

Chen Hujie, Dai Jing

机构信息

Department of Stomatology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434000, P.R. China.

出版信息

Oncol Lett. 2018 Jul;16(1):543-551. doi: 10.3892/ol.2018.8687. Epub 2018 May 10.

Abstract

The aim of the present study is to investigate the role of microRNA (miRNA/miR)-409-3p in the proliferation, invasion and migration of tongue squamous cell carcinoma (TSCC) cells via targeting radixin () gene. The expression of miR-409-3p was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in TSCC tissue and cell lines. The binding of miR-409-3p to was investigated by performing a dual-luciferase reporter gene assay. Tca8113 cells were selected to transfect with miR-409-3p mimic/inhibitor, small interfering (si)-RDX, and miR-409-3p inhibitor + si-RDX, as well as negative control (NC) respectively. The proliferative, migratory and invasive abilities of transfected Tca8113 cells were investigated by cell-counting-kit-8, wound-healing and Transwell assays, respectively. Additionally, a tumor xenograft model was constructed to examine the effects of miR-409-3p on the tumor growth and lymphatic metastasis in nude mice. A significant downregulation was detected in miR-409-3p expression in TSCC tissues and cells (all P<0.05) compared with normal tongue mucosa tissues and cell line, which was associated with lymph node metastasis and tumor-node metastasis staging (both P<0.05). The results from the dual-luciferase reporter gene assay indicated that is a potential target gene of miR-409-3p. Compared with the blank group, a marked reduction in RDX expression, cell proliferation, migration and invasion was detected in the miR-409-3p mimic group and si-RDX group (all P<0.05). Conversely, the reverse was observed in cells that were transfected with the miR-409-3p inhibitor. Furthermore, si-RDX is able to reverse the effect of miR-409-3p inhibitor on cell proliferation, invasion and migration (all P<0.05). The results form the tumor xenograft model of nude mice verified that miR-409-3p mimic is able to inhibit the growth of Tca8113 tumor cells and lymph node metastasis in nude mice. miR-409-3p may delay the proliferation of TSCC cells by inhibiting of so as to decrease its migratory and invasive abilities. Therefore, miR-409-3p may be a potential target for the clinical treatment of TSCC.

摘要

本研究旨在通过靶向根蛋白(Rdx)基因来探究微小RNA(miRNA/miR)-409-3p在舌鳞状细胞癌(TSCC)细胞增殖、侵袭和迁移中的作用。采用逆转录-定量聚合酶链反应(RT-qPCR)检测TSCC组织和细胞系中miR-409-3p的表达。通过双荧光素酶报告基因检测法研究miR-409-3p与Rdx的结合情况。分别选用Tca8113细胞转染miR-409-3p模拟物/抑制剂、小干扰(si)-Rdx、miR-409-3p抑制剂+si-Rdx以及阴性对照(NC)。分别采用细胞计数试剂盒-8、伤口愈合实验和Transwell实验检测转染后Tca8113细胞的增殖、迁移和侵袭能力。此外,构建肿瘤异种移植模型以检测miR-409-3p对裸鼠肿瘤生长和淋巴转移的影响。与正常舌黏膜组织和细胞系相比,TSCC组织和细胞中miR-409-3p表达显著下调(均P<0.05),且与淋巴结转移和肿瘤-淋巴结转移分期相关(均P<0.05)。双荧光素酶报告基因检测结果表明,Rdx是miR-409-3p的潜在靶基因。与空白组相比,miR-409-3p模拟物组和si-Rdx组中Rdx表达、细胞增殖、迁移和侵袭均显著降低(均P<0.05)。相反,转染miR-409-3p抑制剂的细胞中观察到相反的结果。此外,si-Rdx能够逆转miR-409-3p抑制剂对细胞增殖、侵袭和迁移的影响(均P<0.05)。裸鼠肿瘤异种移植模型结果证实,miR-409-3p模拟物能够抑制裸鼠体内Tca8113肿瘤细胞的生长和淋巴结转移。miR-409-3p可能通过抑制Rdx来延缓TSCC细胞的增殖,从而降低其迁移和侵袭能力。因此,miR-409-3p可能是TSCC临床治疗的潜在靶点。

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