目的：探究长链非编码RNA（long non-coding RNA, lncRNA）LINC00308对前列腺癌细胞的增殖、侵袭及迁移的影响及其相关作用机制。方法：利用基因芯片在前列腺癌组织与癌旁对照组织中筛选差异表达的 lncRNA 及 mRNA, 并确定LINC00308 及甲状腺激素受体因子 13（thyroid hormone receptor interactor13，TRIP13）为研究对象。MTT 实验、平板克隆及Transwell和划痕实验检测LINC00308对前列腺癌细胞增殖、侵袭及迁移能力的影响,应用裸鼠移植瘤在体内验证上述影响，应用Western blotting及免疫组化实验在瘤组织和癌细胞中探究LINC00308对TRIP13表达的影响。生物信息学分析技术与RNA免疫共沉淀（RNA immunoprecipitation, RIP）及qPCR和双荧光素酶基因报告实验预测并探究miR-361-5p与LINC00308及TRIP13之间的相互作用机制，并利用平板克隆、Transwell侵袭实验对癌细胞恶性生物行为进行验证。结果：芯片结果及qPCR共同证实LINC00308（P<0.01）与 TRIP13（P<0.05）在前列腺癌组织及 4 种细胞系中均异常高表达 ；细胞功能实验结果表明过表达LINC00308可以促进前列腺癌细胞PC3的增殖、侵袭及迁移能力（均P<0.05），而下调前列腺癌细胞中LINC00308表达起相反作用。裸鼠移植瘤实验证实，LINC00308能够在体内促进前列腺癌PC3细胞的成瘤（P<0.05或P<0.01），且能够在体内体外促进TRIP13 表达（P<0.05）。生物信息学分析与 RIP 及 qPCR 和双荧光素酶基因报告实验结果证实 miR-361-5p 能够分别与LINC00308与TRIP13的3'-UTR靶向结合，且LINC00308能够通过吸附miR-361-5p而作为内源性竞争RNA（competing endoge‐nous RNA，ceRNA）调控TRIP13的表达，MTT、平板克隆及Transwell实验检测癌细胞的增殖、克隆形成和侵袭能力变化证实了三者之间的调控作用。结论：在前列腺癌组织和细胞中异常高表达的LINC00308通过发挥ceRNA的功能抑制miR-361-5p表达而增强TRIP13表达，从而促进前列腺癌的增殖、侵袭及迁移能力。

Objective: To investigate the effect of long non coding RNA (lncRNA) LINC00308 on proliferation, invasion and migration of prostate cancer cells and its related mechanism. Methods: lncRNAs and mRNAs differentially expressed in prostate cancer tissues and adjacent control tissues were screened by gene chip, and LINC00308 and TRIP13 (thyroid hormone receptor interactor13) were identified as the research objects. The effects of LINC00308 on the proliferation, invasion and migration of prostate cancer cells were detected by MTT assay, plate cloning, Transwell and scratch test. The above effects were verified in nude mice xenografts. The effect of LINC00308 on expression of TRIP13 in tumor tissues and cancer cells was detected by Western blotting and immunohistochemistry. Bioinformatics analysis, RIP (RNA immunoprecipitation), qPCR and Double luciferase gene reporter experi‐ments were used to predict and explore the interaction mechanism between miR-361-5p and LINC00308 as well as TRIP13, and plate cloning and Transwell invasion test were used to verify the biological behaviors of cancer cells. Results: Both the microarray results and qPCR confirmed that the expressions of LINC00308 (P<0.01) and TRIP13 (P<0.05) were abnormally high in prostate cancer tis‐sues and four cell lines; cell function test results showed that overexpression of LINC00308 could promote the proliferation, invasion and migration of prostate cancer PC3 cells (all P<0.05), while down-regulation of LINC00308 in prostate cancer cells had the opposite effect. In nude mice. LINC00308 could promote the tumorigenesis of prostate cancer cells in vivo, and increase the expression of TRIP13 both in vivo and in vitro (P<0.05). Bioinformatics analysis, RIP, qPCR and Double luciferase gene reporter results confirmed that miR-361-5p could bind to 3'-UTR of LINC00308 and TRIP13 respectively, and LINC00308 could act as a competing endogenous RNA (ceRNA) by sponging miR-361-5p to regulate the expression of TRIP13. In addition, MTT, plate cloning and Transwell assay confirmed the regulatory interaction among LINC00308 miR-361-5p and TRIP13 from the levels of proliferation, colony formation and invasion in cancer cells. Conclusion: LINC00308, which is abnormally highly expressed in prostate cancer tissues and cells, can inhibit the expression of miR-361-5p and enhance the expression of TRIP13 by exerting its ceRNA function, thus promoting the proliferation,invasion and migration of prostate cancer.

新疆维吾尔自治区自然科学基金项目（No. 2016D01C334）