MicroRNAs in Human Pituitary Adenomas

MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers.

[1]  Kenneth M. Yamada,et al.  Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. , 1999, Cancer research.

[2]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Igaz,et al.  MicroRNA profile indicates downregulation of the TGFβ pathway in sporadic non-functioning pituitary adenomas , 2011, Pituitary.

[4]  K. Vermeulen,et al.  The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer , 2003, Cell proliferation.

[5]  Yonghong Zhu,et al.  A novel marine drug, SZ-685C, induces apoptosis of MMQ pituitary tumor cells by downregulating miR-200c. , 2013, Current Medicinal Chemistry.

[6]  C. Croce,et al.  miR-15 and miR-16 induce apoptosis by targeting BCL2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Xianqun Fan,et al.  Putative tumor suppressor miR‐145 inhibits colon cancer cell growth by targeting oncogene friend leukemia virus integration 1 gene , 2011, Cancer.

[8]  R. Lavker,et al.  MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia , 2008, Proceedings of the National Academy of Sciences.

[9]  B. Scheithauer,et al.  MicroRNA expression in ACTH-producing pituitary tumors: up-regulation of microRNA-122 and -493 in pituitary carcinomas , 2010, Endocrine.

[10]  S. Cory,et al.  The Bcl-2 apoptotic switch in cancer development and therapy , 2007, Oncogene.

[11]  R. Stephenson.  A and V , 1962, The British journal of ophthalmology.

[12]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[13]  V. Ambros.  The functions of animal microRNAs , 2004, Nature.

[14]  E. Kistner,et al.  Let-7 expression defines two differentiation stages of cancer , 2007, Proceedings of the National Academy of Sciences.

[15]  Neil Genzlinger.  A. and Q , 2006 .

[16]  John W M Martens,et al.  Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer , 2008, Proceedings of the National Academy of Sciences.

[17]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[18]  M. Peter,et al.  DEDD, a novel death effector domain‐containing protein, targeted to the nucleolus , 1998, The EMBO journal.

[19]  W. Cho,et al.  MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1 , 2011, RNA biology.

[20]  M. Buchfelder,et al.  Selective loss of somatostatin receptor 2 in octreotide-resistant growth hormone-secreting adenomas. , 2008, The Journal of clinical endocrinology and metabolism.

[21]  A. Paetau,et al.  Gain of chromosome 3 and loss of 13q are frequent alterations in pituitary adenomas. , 2001, Cancer genetics and cytogenetics.

[22]  B. Scheithauer,et al.  Apoptosis in nontumorous and neoplastic human pituitaries: expression of the Bcl-2 family of proteins. , 1999, The American journal of pathology.

[23]  P. Russell,et al.  Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. , 1993, The EMBO journal.

[24]  Yonghong Zhu,et al.  MicroRNA-200c inhibits apoptosis in pituitary adenoma cells by targeting the PTEN/Akt signaling pathway. , 2014, Oncology research.

[25]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[26]  Anindya Dutta,et al.  The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. , 2007, Genes & development.

[27]  Shinji Tanaka,et al.  miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. , 2010, Carcinogenesis.

[28]  A. Fusco,et al.  Nuclear phosphoproteins HMGA and their relationship with chromatin structure and cancer , 2004, FEBS letters.

[29]  Michael T. McManus,et al.  Let-7b/c Enhance the Stability of a Tissue-Specific mRNA during Mammalian Organogenesis as Part of a Feedback Loop Involving KSRP , 2012, PLoS genetics.

[30]  K. Basso,et al.  Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. , 2011, Blood.

[31]  C. Croce,et al.  Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas , 2002, Oncogene.

[32]  H. Samuels,et al.  Induction of PDCD4 tumor suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis , 2004, Oncogene.

[33]  W. Cho,et al.  Abstract 1189: MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1 , 2011 .

[34]  Qin Xu,et al.  miR-300 inhibits epithelial to mesenchymal transition and metastasis by targeting Twist in human epithelial cancer , 2014, Molecular Cancer.

[35]  Zhongwei Cao,et al.  Involvement of miR‐21 in resistance to daunorubicin by regulating PTEN expression in the leukaemia K562 cell line , 2011, FEBS letters.

[36]  C Eng,et al.  PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways. , 2001, Human molecular genetics.

[37]  Kishore Guda,et al.  The noncoding RNA, miR‐126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3‐kinase signaling and is frequently lost in colon cancers , 2008, Genes, chromosomes & cancer.

[38]  Michael Z Michael,et al.  Reduced accumulation of specific microRNAs in colorectal neoplasia. , 2003, Molecular cancer research : MCR.

[39]  D. Molè,et al.  miR-26 a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase C , 2013 .

[40]  C. Croce,et al.  Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1. , 2012, The Journal of clinical endocrinology and metabolism.

[41]  C. Croce,et al.  MicroRNA gene expression deregulation in human breast cancer. , 2005, Cancer research.

[42]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[43]  Giuseppe Giannini,et al.  MiR‐128 up‐regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[44]  Z. Qian,et al.  Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas , 2007, Modern Pathology.

[45]  J. Lachuer,et al.  miR-23b and miR-130b expression is downregulated in pituitary adenomas , 2014, Molecular and Cellular Endocrinology.

[46]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[47]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[48]  Z. Mao,et al.  Differential expression of microRNAs in GH-secreting pituitary adenomas , 2010, Diagnostic pathology.

[49]  K. Chada,et al.  Expression of Mesenchyme-Specific Gene HMGA2 in Squamous Cell Carcinomas of the Oral Cavity , 2004, Cancer Research.

[50]  M. Ceccarelli,et al.  Upregulation of miR-21 by Ras in vivo and its role in tumor growth , 2011, Oncogene.

[51]  J. Steitz,et al.  Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation , 2007, Science.

[52]  加野 将之.  miR-145, miR-133a and miR-133b : tumor suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma , 2010 .

[53]  M. Seto,et al.  Genome‐wide microRNA expression profiling in renal cell carcinoma: significant down‐regulation of miR‐141 and miR‐200c , 2008, The Journal of pathology.

[54]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[55]  A. Barkan,et al.  Pituitary Disorders , 2012, Drugs.

[56]  Vincent Moulton,et al.  Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level. , 2010, RNA.

[57]  David P. Bartel,et al.  Supporting Online Material Materials and Methods Fig. S1 Tables S1 and S2 References Database S1 Disrupting the Pairing between Let-7 and Hmga2 Enhances Oncogenic Transformation , 2022 .

[58]  X. Chen,et al.  Role of miR-143 targeting KRAS in colorectal tumorigenesis , 2009, Oncogene.

[59]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[60]  H. Wu,et al.  PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[61]  X. Agirre,et al.  Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues , 2006, Molecular Cancer.

[62]  W. Marsden.  I and J , 2012 .

[63]  A. Sánchez-Aguilera,et al.  Cell cycle deregulation in B-cell lymphomas. , 2003, Blood.

[64]  I. Faraoni,et al.  miR-155 gene: a typical multifunctional microRNA. , 2009, Biochimica et biophysica acta.

[65]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.

[66]  F. Saggioro,et al.  MicroRNAs differentially expressed in ACTH-secreting pituitary tumors. , 2009, The Journal of clinical endocrinology and metabolism.

[67]  Tianhua Zhou,et al.  Down-regulation of miR-141 in gastric cancer and its involvement in cell growth , 2009, Journal of Gastroenterology.

[68]  Y. Mo,et al.  Systematic validation of predicted microRNAs for cyclin D1 , 2009, BMC Cancer.

[69]  George A Calin,et al.  Identification of differentially expressed microRNAs by microarray: A possible role for microRNA genes in pituitary adenomas , 2007, Journal of cellular physiology.

[70]  Jian Lu,et al.  Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. , 2013, The Lancet. Oncology.

[71]  R. Mantovani,et al.  Transcriptional Activation of the Cyclin A Gene by the Architectural Transcription Factor HMGA2 , 2003, Molecular and Cellular Biology.

[72]  B. Scheithauer,et al.  Frequent loss of heterozygosity at the retinoblastoma susceptibility gene (RB) locus in aggressive pituitary tumors: evidence for a chromosome 13 tumor suppressor gene other than RB. , 1995, Cancer research.

[73]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[74]  B. Bartel.  MicroRNAs directing siRNA biogenesis , 2005, Nature Structural &Molecular Biology.

[75]  C. Croce,et al.  The High Mobility Group A2 gene is amplified and overexpressed in human prolactinomas. , 2002, Cancer research.

[76]  S. Asa,et al.  Mechanisms of Disease: the pathogenesis of pituitary tumors , 2006, Nature Clinical Practice Endocrinology &Metabolism.

[77]  P. Igaz,et al.  Down-regulation of Wee1 kinase by a specific subset of microRNA in human sporadic pituitary adenomas. , 2010, The Journal of clinical endocrinology and metabolism.

[78]  Dashi Zhi,et al.  The experimental study of miRNA in pituitary adenomas. , 2013, Turkish neurosurgery.

[79]  Z. Qian,et al.  Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas , 2009, Modern Pathology.

[80]  M. Korbonits,et al.  MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro. , 2012, American journal of physiology. Endocrinology and metabolism.

[81]  Agnieszka Bronisz,et al.  Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. , 2008, Cancer research.

[82]  R. Mason,et al.  TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT) , 2005, Respiratory research.

[83]  Chunxiang Zhang,et al.  The miR-143/145 Cluster Is a Novel Transcriptional Target of Jagged-1/Notch Signaling in Vascular Smooth Muscle Cells* , 2011, The Journal of Biological Chemistry.

[84]  A. Fusco,et al.  Roles of HMGA proteins in cancer , 2007, Nature Reviews Cancer.

[85]  B. Scheithauer,et al.  Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. , 2008, Endocrine-related cancer.

[86]  Arianna Bottoni,et al.  miR‐15a and miR‐16‐1 down‐regulation in pituitary adenomas , 2005, Journal of cellular physiology.

[87]  Zichao Zhang,et al.  MicroRNAs Regulate Pituitary Development, and MicroRNA 26b Specifically Targets Lymphoid Enhancer Factor 1 (Lef-1), Which Modulates Pituitary Transcription Factor 1 (Pit-1) Expression* , 2010, The Journal of Biological Chemistry.

[88]  D. Tong,et al.  HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer. , 2005, Oncology reports.

[89]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[90]  V. Kim,et al.  MicroRNA maturation: stepwise processing and subcellular localization , 2002, The EMBO journal.

[91]  Ralph Weissleder,et al.  MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. , 2007, Cancer research.

[92]  Y. Akao,et al.  let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. , 2006, Biological & pharmaceutical bulletin.

[93]  C. Mayr,et al.  miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely , 2007, Proceedings of the National Academy of Sciences.

[94]  R. Thakker,et al.  Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker. , 1997, The Journal of clinical endocrinology and metabolism.

[95]  G. Weiss,et al.  MicroRNAs and cancer: past, present, and potential future , 2008, Molecular Cancer Therapeutics.

[96]  Masayuki Kano,et al.  miR‐145, miR‐133a and miR‐133b: Tumor‐suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma , 2010, International journal of cancer.

[97]  A. Gartel,et al.  miRNAs: Little known mediators of oncogenesis. , 2008, Seminars in cancer biology.

[98]  Mauro Biffoni,et al.  The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities , 2008, Nature Medicine.

[99]  D. Molè,et al.  miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ , 2013, Endocrinology.

[100]  本山 一夫.  Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family , 2009 .

[101]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[102]  Libing Song,et al.  Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer , 2011, Molecular Cancer.

[103]  D. Iliopoulos,et al.  Functional screen analysis reveals miR-26b and miR-128 as central regulators of pituitary somatomammotrophic tumor growth through activation of the PTEN–AKT pathway , 2013, Oncogene.

[104]  H. Allgayer,et al.  MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer , 2008, Oncogene.

[105]  S. Asa,et al.  The pathogenesis of pituitary tumours , 2002, Nature Reviews Cancer.

[106]  N. Webster,et al.  Gonadotropin-releasing hormone induces miR-132 and miR-212 to regulate cellular morphology and migration in immortalized LbetaT2 pituitary gonadotrope cells. , 2011, Molecular endocrinology.

[107]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[108]  Muller Fabbri,et al.  A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. , 2005, The New England journal of medicine.