Chang Liang, Hu Zhuang, Zhou Zhenyu, Zhang Hui
Department of Thyroid Breast Surgery, Huaihe Hospital of Henan University No. 115, Ximen Street, Gulou District Kaifeng 475000 China
Department of Gastroenterology, Huaihe Hospital of Henan University Kaifeng 475000 China.
RSC Adv. 2018 Apr 24;8(27):15229-15240. doi: 10.1039/c8ra02090f. eCollection 2018 Apr 18.
: Dysregulated lncRNA expression contributes to the pathogenesis of human tumors the lncRNAs functioning as oncogenes or tumor suppressors. Small nucleolar RNA host gene 3 (SNHG3) was demonstrated to be upregulated in breast cancer cells. However, the detailed roles and molecular mechanism of SNHG3 in breast cancer are largely unknown. : The expression of SNHG3, miR-101, and zinc finger E-box-binding protein 1 (ZEB1) in breast cancer tissues and cells was detected using qRT-PCR. The effects of SNHG3 on cell proliferation and invasion were evaluated using MTT, EdU, and cell invasion assays. The protein levels of Ki-67, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase MMP-2, and MMP-9 were analyzed using western blot analysis. A luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to explore the interaction between SNHG3, ZEB1 and miR-101. A subcellular fractionation assay was used to detect the subcellular location of SNHG3. Xenograft tumor experiments were conducted to verify the role and mechanism of SNHG3 in breast cancer . : SNHG3 expression was upregulated in breast cancer tissues and correlated with poor prognosis. SNHG3 knockdown suppressed breast cancer cell proliferation and invasion, which was further demonstrated by high levels of proliferation marker proteins Ki-67/PCNA and metastasis-related proteins MMP-2/MMP-9. Additionally, SNHG3 was located in the cytoplasm of breast cancer cells. SNHG3 functioned as a molecular sponge for miR-101 in breast cancer cells. miR-101 was downregulated in breast cancer tissues and negatively correlated with SNHG3 expression. Moreover, ZEB1, a target of miR-101, was positively regulated by SNHG3 in breast cancer cells. ZEB1 mRNA expression was upregulated in breast cancer tissues and positively correlated with SNHG3 expression. Mechanistically, SNHG3 knockdown suppressed cell proliferation and invasion by upregulation of miR-101 and downregulation of ZEB1 expression in breast cancer cells and . : SNHG3 promoted proliferation and invasion by regulating the miR-101/ZEB1 axis in breast cancer.
长链非编码RNA（lncRNA）表达失调参与人类肿瘤的发病机制，lncRNAs可作为癌基因或肿瘤抑制因子发挥作用。小核仁RNA宿主基因3（SNHG3）在乳腺癌细胞中被证明上调。然而，SNHG3在乳腺癌中的具体作用和分子机制尚不清楚。
采用qRT-PCR检测乳腺癌组织和细胞中SNHG3、miR-101和锌指E盒结合蛋白1（ZEB1）的表达。采用MTT、EdU和细胞侵袭实验评估SNHG3对细胞增殖和侵袭的影响。采用蛋白质印迹分析检测Ki-67、增殖细胞核抗原（PCNA）、基质金属蛋白酶MMP-2和MMP-9的蛋白水平。进行荧光素酶报告基因实验和RNA免疫沉淀（RIP）以探究SNHG3、ZEB1和miR-101之间的相互作用。采用亚细胞分级分离实验检测SNHG3的亚细胞定位。进行异种移植肿瘤实验以验证SNHG3在乳腺癌中的作用和机制。
SNHG3在乳腺癌组织中表达上调，且与预后不良相关。SNHG3敲低抑制乳腺癌细胞增殖和侵袭，增殖标志物蛋白Ki-67/PCNA和转移相关蛋白MMP-2/MMP-9水平升高进一步证明了这一点。此外，SNHG3定位于乳腺癌细胞的细胞质中。SNHG3在乳腺癌细胞中作为miR-101的分子海绵发挥作用。miR-101在乳腺癌组织中下调，且与SNHG3表达呈负相关。此外，作为miR-101靶标的ZEB1在乳腺癌细胞中受到SNHG3的正调控。ZEB1 mRNA表达在乳腺癌组织中上调，且与SNHG3表达呈正相关。机制上，SNHG3敲低通过上调miR-101和下调乳腺癌细胞中ZEB1表达抑制细胞增殖和侵袭。
SNHG3通过调节miR-101/ZEB1轴促进乳腺癌增殖和侵袭。
