miR-200b as a prognostic factor targets multiple members of RAB family in glioma

AbstractmiR-200b is a tumor suppressor in multiple tumors including gastric cancer, breast cancer, ovarian cancer and glioma. In this study, we detected the expression of miR-200b and analyzed its correlation with clinicopathological parameters in glioma tissues. miR-200b was downregulated in glioma tissues. And its downexpression was correlated with poor prognosis in gliomas. Members of RAB family, RAB21, RAB23, RAB18 and RAB3B were predicted to be novel targets of miR-200b. The direct suppression of RAB21, RAB23, RAB18 and RAB3B expressions by miR-200b was revealed by luciferase reporter assay, quantitative RT-PCR analysis and Western blot. Furthermore, the overall survival of patients with different expression of RABs was analyzed. The expression of RAB21, RAB23, RAB18 and RAB3B was related to the prognosis and histopathology of glioma. The patients who had the upregulation of all the four RABs had the worst outcome; those who had the downregulation of all RABs had the best outcome (p < 0.001). miR-200b was a potential biomarker for glioma prognosis.

[1]  David N Louis,et al.  Molecular pathology of malignant gliomas. , 2006, Annual review of pathology.

[2]  R. Pepperkok,et al.  Rab18 and Rab43 have key roles in ER-Golgi trafficking , 2008, Journal of Cell Science.

[3]  M. Malagón,et al.  Rab18 is reduced in pituitary tumors causing acromegaly and its overexpression reverts growth hormone hypersecretion. , 2008, The Journal of clinical endocrinology and metabolism.

[4]  G. Goodall,et al.  The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 , 2008, Nature Cell Biology.

[5]  Siew Hong Leong,et al.  Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. , 2008, Cancer research.

[6]  M. Korpal,et al.  The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2* , 2008, Journal of Biological Chemistry.

[7]  R. Parton,et al.  Characterization of Rab18, a lipid droplet-associated small GTPase. , 2008, Methods in enzymology.

[8]  K. Aldape,et al.  Beyond grade: molecular pathology of malignant gliomas. , 2009, Seminars in radiation oncology.

[9]  E. Howe,et al.  Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers , 2009, Journal of oncology.

[10]  Hongmei Ding,et al.  MicroRNA-200b regulates cyclin D1 expression and promotes S-phase entry by targeting RND3 in HeLa cells , 2010, Molecular and Cellular Biochemistry.

[11]  E. Sahai,et al.  A chemical biology screen reveals a role for Rab21-mediated control of actomyosin contractility in fibroblast-driven cancer invasion , 2009, British Journal of Cancer.

[12]  B. Martínez-Delgado,et al.  The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients. , 2010, Endocrine-related cancer.

[13]  François Radvanyi,et al.  Deregulation of Rab and Rab Effector Genes in Bladder Cancer , 2012, PloS one.

[14]  CpG island hypermethylation-associated silencing of microRNAs promotes human endometrial cancer , 2013, Cancer Cell International.

[15]  Gregory J Goodall,et al.  Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem-cell-like state , 2013, Journal of Cell Science.

[16]  Hai-bo Wu,et al.  Aberrant expression of microRNAs involved in epithelial–mesenchymal transition of HT‐29 cell line , 2013, Cell biology international.

[17]  Fen Yang,et al.  miR-200b targets GATA-4 during cell growth and differentiation , 2013, RNA biology.

[18]  C. Klinge,et al.  Reduced Expression of miR-200 Family Members Contributes to Antiestrogen Resistance in LY2 Human Breast Cancer Cells , 2013, PloS one.

[19]  Yawei Liu,et al.  Down‐regulation of miR‐200b‐3p by low p73 contributes to the androgen‐independence of prostate cancer cells , 2013, The Prostate.

[20]  Chuanlu Jiang,et al.  RAB38 confers a poor prognosis, associated with malignant progression and subtype preference in glioma. , 2013, Oncology reports.

[21]  Anla Hu,et al.  Effects of Rab27a on proliferation, invasion, and anti-apoptosis in human glioma cell , 2013, Tumor Biology.

[22]  Min Deng,et al.  miR-200b and miR-200c as Prognostic Factors and Mediators of Gastric Cancer Cell Progression , 2013, Clinical Cancer Research.

[23]  Jun Zhan,et al.  Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family , 2013, International journal of cancer.

[24]  V. Castranova,et al.  The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells , 2013, International journal of oncology.

[25]  James Lee,et al.  Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells , 2013, Journal of Cell Science.

[26]  Tao Zhang,et al.  Hepatitis B virus X protein upregulates oncogene Rab18 to result in the dysregulation of lipogenesis and proliferation of hepatoma cells. , 2013, Carcinogenesis.

[27]  W. Westbroek,et al.  Vacuolar H+ ATPase expression and activity is required for Rab27B‐dependent invasive growth and metastasis of breast cancer , 2013, International journal of cancer.

[28]  N. Seki,et al.  Epithelial–mesenchymal transition-related microRNA-200s regulate molecular targets and pathways in renal cell carcinoma , 2013, Journal of Human Genetics.

[29]  Biao PengSu.  MicroRNA-200b targets CREB1 and suppresses cell growth in human malignant glioma , 2013 .