[摘要] 目的：探讨lncRNA MALAT1 通过调控miR-124-3p/IGF2BP1 分子轴介导宫颈癌细胞增殖和转移的影响。方法：选取2014 年4 月至2017 年12 月在贵阳市妇幼保健院妇产科收治的、经手术切除的45 例宫颈癌患者癌组织及相应癌旁组织标本，以及宫颈癌细胞系SiHa、Caski、HeLa 和C33a，采用qPCR法检测癌组织和癌细胞系中MALAT1 的表达水平。构建MALAT1 敲降载体、miR-124-3p inhibitor 及IGF2BP1 过表达载体转染宫颈癌细胞，采用CCK-8、Transwell、Wb及免疫荧光实验探讨MALAT1 或其敲降后通过miR-124-3p/IGF2BP1 分子轴对宫颈癌细胞增殖、侵袭和上皮间质转化的影响。采用双荧光素酶报告基因检测lncRNA MALAT1、miR-124-3p 及IGF2BP1 的靶向调控关系。结果：MALAT1 在宫颈癌组织和细胞系中高表达（P<0.05 或P<0.01）。同时，敲降MALAT1 显著抑制宫颈癌细胞增殖、侵袭和上皮间质转化（P<0.05 或P<0.01）。双荧光素酶报告基因证实MALAT1 靶向作用miR-124-3p 并下调其表达水平，miR-124-3p 可负调控IGF2BP1 的表达。实验进一步证实敲降MALAT1 通过靶向上调miR-124-3p 对IGF2BP1 的抑制作用，进而抑制宫颈癌细胞增殖、侵袭和上皮间质转化（P<0.05 或P<0.01）。结论：lncRNA MALAT1 通过下调miR-124-3p/IGF2BP1 分子轴促进宫颈癌细胞增殖、侵袭和上皮间质转化，为临床宫颈癌早期诊断/治疗提供了潜在的分子靶点。

[Abstract] Objective: To investigate the mechanism of lncRNA MALAT1 modulating proliferation and metastasis of cervical cancer cells via regulating miR-124-3p/IGF2BP1 axis. Methods: A total of 45 cases of cervical cancer tissues and corresponding paracancerous tissues resected from patients, who were admitted to the Department of Obstetrics and Gynecology of Guiyang Maternal and Child Health Hospital during April 2014 and December 2017, were included in this study; in addition, cervical cancer cell lines SiHa, Caski,HeLa and C33awere also collected for this study. qPCR was applied to detect the expression of MALAT1 in cervical cancer tissues and cell lines. MALAT1-knockdown vectors, miR-124-3p inhibitors and IGF2BP1-overexpression vectors were constructed and used to transfect cervical cancer cells, respectively; the influence of MALAT1 or MALAT1 knockdown on cell proliferation, invasion and epithelial mesenchymal transition (EMT) via miR-124-3p/IGF2BP1 axis were determined by CCK-8 assay, Transwell assay, Wb and immunofluorescence,respectively. The interaction between MALAT1, miR-124-3p, and IGF2BP1 were verified by dual luciferase reporter gene assay. Results: MALAT1 was up-regulated in cervical cancer tissues and cell lines (P<0.05 or P<0.01). Meanwhile, MALAT1 knockdown remarkably inhibited proliferation, invasion and EMT of cervical cancer cells (P<0.05 or P<0.01). Moreover, dual-luciferase reporter gene assay showed that MALAT1 directly interacted with miR-124-3p and down-regulated its expression, while miR-124-3p negatively regulated IGF2BP1 expression. Our experiment further validated that MALAT1 knockdown suppressed proliferative, invasion and EMT of cervical cancer cells via inducing the inhibitory effect of miR-124-3p on IGF2BP1 (P<0.05 or P<0.01). Conclusion:MALAT1 promotes the proliferation, invasion and EMT of cervical cancer cells by down-regulating miR-124-3p/IGF2BP1 axis,which provides potential molecular targets for early diagnosis or treatment of cervical cancer.

国家自然科学基金资助项目（No.81560287）