SNHG3 promotes migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the miR-186-5p/ZEB1 axis.

Increasing evidence suggests that the long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. The lncRNA small nucleolar RNA host gene 3 (SNHG3) reportedly acts as an oncogene in hepatocellular carcinoma and colorectal cancer; however, little is known about the biological function and oncogenic mechanisms of SNHG3 in breast cancer. We demonstrated that the expression of SNHG3 was abnormally high in breast cancer tissues and cells, and transgenic expression of SNHG3 promoted the proliferation, migration, and invasion of breast cancer cell lines (MCF-7 and MDA-MB-231). The mean volume of the xenografts from the SNHG3-knockdown MCF-7 cells was lower than that of the control tumor cells. Moreover, the expression of zinc finger E-box binding homeobox 1 (ZEB1) increased after SNHG3 overexpression and vice versa. Overexpression of ZEB1 triggered cellular migration and invasion behaviors. Analysis of the mechanism underlying these effects suggested that SNHG3 is an effective sink for miR-186-5p and modulates ZEB1 repression, conferring an additional level to its post-transcriptional regulation. In conclusion, SNHG3 promotes the migration and invasion of breast cancer cells through miR-186-5p/ZEB1 regulation and the induction of the epithelial to mesenchymal transition, indicating that SNHG3 is a potential treatment target for breast cancer.

[1]  E. Ségal-Bendirdjian,et al.  The long non coding RNA H19 as a biomarker for breast cancer diagnosis in Lebanese women , 2020, Scientific Reports.

[2]  L. Jingjing,et al.  LncRNA SNHG3 promotes the growth and metastasis of colorectal cancer by regulating miR-539/RUNX2 axis. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[3]  Yong Zhou,et al.  NEAT1 contributes to breast cancer progression through modulating miR‐448 and ZEB1 , 2018, Journal of cellular physiology.

[4]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[5]  A. Ke,et al.  LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR‐128/CD151 pathway in hepatocellular carcinoma , 2018, Journal of cellular physiology.

[6]  X. Zhan,et al.  The lncRNA SNHG3 regulates energy metabolism of ovarian cancer by an analysis of mitochondrial proteomes. , 2018, Gynecologic oncology.

[7]  E. Giovannetti,et al.  TGF-β induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression , 2018, Nature Communications.

[8]  L. Xia,et al.  MiR-186-5p upregulation inhibits proliferation, metastasis and epithelial-to-mesenchymal transition of colorectal cancer cell by targeting ZEB1. , 2018, Archives of biochemistry and biophysics.

[9]  Bin Xia Yang,et al.  LncRNA HULC promotes epithelial and smooth-muscle-like differentiation of adipose-derived stem cells by upregulation of BMP9. , 2018, Die Pharmazie.

[10]  Di Chen,et al.  Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin‐6/STAT3 signaling pathway , 2018, Hepatology.

[11]  Xiaohua Liu,et al.  RUNX3 plays an important role in mediating the BMP9-induced osteogenic differentiation of mesenchymal stem cells. , 2017, International journal of molecular medicine.

[12]  I. Ulitsky,et al.  The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element , 2017, Genome Biology.

[13]  Jun Li,et al.  The long non-coding RNA SNHG3 functions as a competing endogenous RNA to promote malignant development of colorectal cancer , 2017, Oncology reports.

[14]  Bai-Cheng He,et al.  Follicle‐Stimulating Hormone β‐Subunit Potentiates Bone Morphogenetic Protein 9‐Induced Osteogenic Differentiation in Mouse Embryonic Fibroblasts , 2017, Journal of cellular biochemistry.

[15]  Kewei Ren,et al.  Long non‐coding RNA H19 promotes the proliferation and invasion of breast cancer through upregulating DNMT1 expression by sponging miR‐152 , 2017, Journal of biochemical and molecular toxicology.

[16]  Xiaolong Wang,et al.  SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. , 2017, Biochemical and biophysical research communications.

[17]  Ke Wang,et al.  Inhibitory effects of BMP9 on breast cancer cells by regulating their interaction with pre-adipocytes/adipocytes , 2017, Oncotarget.

[18]  Z. Zeng,et al.  Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer , 2017, Molecular Cancer.

[19]  Benjamin Haibe-Kains,et al.  The molecular basis of breast cancer pathological phenotypes , 2017, The Journal of pathology.

[20]  Yan Zhang,et al.  MALAT1 induced migration and invasion of human breast cancer cells by competitively binding miR-1 with cdc42. , 2016, Biochemical and biophysical research communications.

[21]  C. Iacobuzio-Donahue,et al.  TGF-β Tumor Suppression through a Lethal EMT , 2016, Cell.

[22]  Pu Zhang,et al.  BMP9/p38 MAPK is essential for the antiproliferative effect of resveratrol on human colon cancer. , 2016, Oncology reports.

[23]  Bing Li,et al.  LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p. , 2016, Cancer letters.

[24]  Li Liu,et al.  SNHG3 correlates with malignant status and poor prognosis in hepatocellular carcinoma , 2016, Tumor Biology.

[25]  I. Fabregat,et al.  BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation , 2015, International journal of molecular sciences.

[26]  T. Brabletz,et al.  The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5 , 2015, Oncotarget.

[27]  R. Haydon,et al.  Bone Morphogenetic Protein (BMP) signaling in development and human diseases , 2014, Genes & diseases.

[28]  Qun Zhou,et al.  Long non-coding RNAs in stem cells and cancer. , 2014, World journal of clinical oncology.

[29]  Tongchuan He,et al.  BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways , 2014, PloS one.

[30]  Hui Zhou,et al.  starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data , 2013, Nucleic Acids Res..

[31]  V. Brunton,et al.  E-cadherin–integrin crosstalk in cancer invasion and metastasis , 2013, Journal of Cell Science.

[32]  Martin Reczko,et al.  DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs , 2012, Nucleic Acids Res..

[33]  T. Visakorpi,et al.  Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer , 2012, Oncogene.

[34]  T. He,et al.  BMP9 inhibits the proliferation and invasiveness of breast cancer cells MDA-MB-231 , 2011, Journal of Cancer Research and Clinical Oncology.

[35]  Howard Y. Chang,et al.  A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression , 2011, Nature.

[36]  J. Ragoussis,et al.  The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis , 2011, British Journal of Cancer.

[37]  Chi-Hung Huang,et al.  Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition , 2010, Nature Cell Biology.

[38]  R. Huang,et al.  Epithelial-Mesenchymal Transitions in Development and Disease , 2009, Cell.

[39]  Raghu Kalluri,et al.  The basics of epithelial-mesenchymal transition. , 2009, The Journal of clinical investigation.

[40]  H. You,et al.  Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression , 2009, Molecular and Cellular Biology.

[41]  Carlos Caldas,et al.  Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis , 2007, Nature Reviews Cancer.

[42]  D. Dean,et al.  Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[43]  A. Jemal,et al.  Cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[44]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.