肿瘤相关巨噬细胞外泌体lnc-SLC2A12-10:1调节miR-296-5p促进乳腺癌细胞增殖、侵袭

Long non-coding RNA lnc-SLC2A12-10:1 derived from tumor-associated macrophage exosome aggravates the proliferation and invasion of breast cancer cells through miR-296-5p

目的探讨肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)外泌体中lnc-SLC2A12-10:1对乳腺癌(breast cancer,BC)细胞增殖、侵袭的影响及其机制。方法GEO芯片分析BC中差异表达的lnc-SLC2A12-10:1,qRT-PCR测定lnc-SLC2A12-10:1、miR-296-5p在组织和细胞中的表达。分离TAMs及外泌体。干预外泌体中lnc-SLC2A12-10:1及细胞中的miR-296-5p的表达后借助MTT、Transwell试验检测细胞增殖及侵袭情况。结果相对于癌旁组织,lnc-SLC2A12-10:1在BC组织中显著上调(t=7.09,P<0.001)。与正常乳腺细胞比较,T47D、MDA-MB-468细胞中lnc-SLC2A12-10:1的表达均明显上调(t=9.90,P<0.001)(t=12.18,P<0.001)。lnc-SLC2A12-10:1能作为miR-296-5p的ceRNA。敲减lnc-SLC2A12-10:1能够抑制BC细胞增殖、侵袭,miR-296-5p-inhibitor能促进BC细胞增殖、侵袭,但该作用能被si-lnc-SLC2A12-10:1-Exo部分挽救(均P<0.05)。结论TAMs外泌体中携带的lnc-SLC2A12-10:1能促进BC细胞增殖、侵袭,从而推进BC的进展。

Objective To investigate the effect of the mechanism of lnc-SLC2A12-10:1 derived from tumor-associated macrophages(TAMs)exosomes on the proliferation and invasion of breast cancer(BC)cells.Methods GEO microarray analysis was used to screen out the differentially expressed lnc-SLC2A12-10:1 in BC.qRT-PCR was performed to determine the expression level of lnc-SLC2A12-10:1 and miR-296-5p in tissue and cells.Then TAMs and exosomes were isolated.After,interfering the expression level of lnc-SLC2A12-10:1 in exosomes and miR-296-5p expression in cells,then cell proliferation and invasion were detected with the help of MTT and Transwell assays.Results Compared with adjacent tissues,lnc-SLC2A12-10:1 was significantly up-regulated in BC tissues(t=7.09,P<0.001).Compared with normal breast cells,the expression of lnc-SLC2A12-10:1 in T47D and MDA-MB-468 cells was significantly up-regulated(t=9.90,P<0.001)(t=12.18,P<0.001).lnc-SLC2A12-10:1 could act as a ceRNA of miR-296-5p.Knockdown of lnc-SLC2A12-10:1 inhibited BC cell proliferation and invasion,miR-296-5p inhibitor promoted BC cell proliferation and invasion,but this effect could be partially rescued by si--lnc-SLC2A12-10:1-Exo(all P<0.05).Conclusion lnc-SLC2A12-10:1 derived from TAMs exosomes promotes BC cell proliferation,invasion and thus advance BC progression.