KCNQ1OT1 promotes migration and inhibits apoptosis by modulating miR-185-5p/Rab14 axis in oral squamous cell carcinoma
KCNQ1OT1 promotes migration and inhibits apoptosis by modulating miR-185-5p/Rab14 axis in oral squamous cell carcinoma
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DOI：
10.1111/dgd.12638
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发表时间：
2019-12-01
影响因子：
2.5
通讯作者：
Ding, Nan
中科院分区：
文献类型：
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作者：
Bao, Qiyan;Liao, Xiangling;Ding, Nan
长非编码RNAs(Long Non-Coding RNAs，LncRNAs)通过与microRNA相互作用，在肿瘤发生和转移的基因转录调控中发挥重要作用。本研究探讨了LncRNA KCNQ1OT1和miR-185-5p在口腔鳞状细胞癌(OSCC)细胞中的表达和功能。采用qRT-PCR方法检测KCNQ1OT1在口腔鳞癌组织和细胞中的表达。利用针对KCNQ1OT1的小干扰RNA(si-KCNQ1OT1)在口腔鳞癌细胞中敲除KCNQ1OT1。通过创面愈合实验、Transwell实验和细胞凋亡检测来评估细胞功能。荧光素酶分析证实了KCNQ1OT1与miR-185-5P的结合区。QRT-PCR法检测MIR-185-5p的表达。通过荧光素酶活性测定，确定Rab14为miR-185-5p的下游靶基因。Western印迹法检测转染miR-185-5p或si-KCNQ1OT1的口腔鳞癌细胞中Rab14蛋白的表达水平。同时检测si-KCNQ1OT1和miR-185-5p抑制剂共转染后口腔鳞状细胞癌细胞功能和Rab14表达的变化。KCNQ1OT1在口腔鳞癌组织和细胞中表达上调。KCNQ1OT1沉默抑制口腔鳞癌细胞恶性，下调miR-185-5p在口腔鳞癌组织中的表达。Rab14作为miR-185-5p的靶基因，在口腔鳞癌中高表达。KCNQ1OT1基因敲除可削弱口腔鳞癌细胞的侵袭能力，促进细胞凋亡，抑制Rab14的表达。在KCNQ1OT1沉默细胞中，miR-185-5p的抑制逆转了Rab14的抑制，恢复了口腔鳞癌细胞的癌细胞生长。提示KCNQ1OT1通过调节miR-185-5p/Rab14轴促进口腔鳞癌的发生，可能成为治疗口腔鳞癌的靶点。
Long non-coding RNAs (lncRNAs) play essential roles in the regulation of gene transcription in carcinogenesis and metastasis via interacting with microRNA. In this study, we explored the expressions and functions of lncRNA KCNQ1OT1 and miR-185-5p in oral squamous cell carcinoma (OSCC) cells. KCNQ1OT1 expression in OSCC tissues and cells was examined by qRT-PCR. Small interfering RNAs against KCNQ1OT1 (si- KCNQ1OT1) were used to knockdown KCNQ1OT1 in OSCC cells. Cell function was assessed by wound healing assay, transwell assay, and apoptosis detection. The binding region between KCNQ1OT1 and miR-185-5p was confirmed by luciferase assays. MiR-185-5p expression was measured by qRT-PCR. Rab14 was confirmed as a downstream target gene of miR-185-5p by measuring luciferase activities. The protein level of Rab14 in OSCC cells transfected with miR-185-5p or si-KCNQ1OT1 was determined by Western blot. The OSCC cell function and Rab14 expression after co-transfection of si-KCNQ1OT1 and miR-185-5p inhibitor were also examined. KCNQ1OT1 was upregulated in OSCC tissues and cells. KCNQ1OT1 silencing suppressed OSCC cell malignancy and downregulated miR-185-5p level, which showed upregulated expression in OSCC samples. Rab14 as a target gene of miR-185-5p was highly expressed in OSCC. KCNQ1OT1 knockdown impaired the invasion capability of OSCC cells, promoted apoptosis, and suppressed Rab14 expression. The inhibition of miR-185-5p in KCNQ1OT1 silencing cells reversed the suppression of Rab14 and restored the cancerous growth of OSCC cells. These results indicated that KCNQ1OT1 promoted OSCC tumorigenesis via the modulation of miR-185-5p/Rab14 axis, which may serve as a therapeutic target for the treatment of OSCC.