Xia Wenfei, Liu Yun, Cheng Teng, Xu Tao, Dong Menglu, Hu Xiaopeng
Department of Breast and Thyroid Surgery, Division of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of ENT, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cell Dev Biol. 2021 Jun 25;9:628573. doi: 10.3389/fcell.2021.628573. eCollection 2021.
Breast cancer (BC) represents the most commonly diagnosed malignancy among women. Long non-coding RNAs (lncRNAs) can be transferred by extracellular vesicles (EVs) to participate in BC progression. This study demonstrated that SNHG16 expression was significantly increased in BC tissues and cells. Overexpression of SNHG16 promoted the migration, invasion, and epithelial-mesenchymal transition (EMT) of BC cells. SNHG16 was carried by EVs. Bioinformatics analysis predicted that SNHG16 regulated PPAPDC1A expression by sponging miR-892b, which was confirmed by RNA-fluorescence hybridization (FISH), RT-qPCR, dual-luciferase gene reporter assay, and RNA immunoprecipitation (RIP). MDA-MB-157 and HS578T cells were transfected with pcDNA3.1-SNHG16, miR-892b-mimic, or si-PPAPDC1A for functional rescue experiments , and the cells were treated with MDA-MB-231 cell-derived EVs. The results confirmed that enhanced miR-892b expression partially eliminated the increase of migration, invasion, and EMT of BC cells mediated by SNHG16 or EVs. The lung metastasis model in nude mice was established by injecting HS578T cells tail vein. The results showed that si-SNHG16 reduced the metastatic nodules and decreased the vimentin expression. In conclusion, EVs derived from BC cells transferred SNHG16 the miR-892b/PPAPDC1A axis, thus promoting EMT, migration, and invasion of BC.
乳腺癌(BC)是女性中最常被诊断出的恶性肿瘤。长链非编码RNA(lncRNAs)可通过细胞外囊泡(EVs)进行转移,从而参与乳腺癌的进展。本研究表明,SNHG16在乳腺癌组织和细胞中的表达显著增加。SNHG16的过表达促进了乳腺癌细胞的迁移、侵袭和上皮-间质转化(EMT)。SNHG16由细胞外囊泡携带。生物信息学分析预测,SNHG16通过海绵吸附miR-892b来调节PPAPDC1A的表达,这一点通过RNA荧光杂交(FISH)、RT-qPCR、双荧光素酶基因报告分析和RNA免疫沉淀(RIP)得到了证实。将pcDNA3.1-SNHG16、miR-892b模拟物或si-PPAPDC1A转染到MDA-MB-157和HS578T细胞中进行功能挽救实验,并用MDA-MB-231细胞来源的细胞外囊泡处理这些细胞。结果证实,增强的miR-892b表达部分消除了由SNHG16或细胞外囊泡介导的乳腺癌细胞迁移、侵袭和EMT的增加。通过尾静脉注射HS578T细胞建立裸鼠肺转移模型。结果表明,si-SNHG16减少了转移结节并降低了波形蛋白的表达。总之,乳腺癌细胞来源的细胞外囊泡通过miR-892b/PPAPDC1A轴转移SNHG16,从而促进乳腺癌的EMT、迁移和侵袭。