title: Up-regulation of microRNA-21 correlates with lower kidney cancer survival.
abstract: BACKGROUND
  MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically.
  
  
  RESULTS
  We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR. The expression level of miR-21 was correlated with 5 year survival and the pathological stage. Functional studies were done after inhibiting miR-21 in RCC cell lines. We studied in vitro and in vivo effects of the chemo preventive agent genistein on miR-21 expression. In 48 cases (90%), miR-21 was increased. All patients with low miR-21 expression survived 5 years, while with high miR-21 expression, only 50% survived. Higher expression of miR-21 is associated with an increase in the stage of renal cancer. Functional studies after inhibiting miRNA-21 in RCC cell lines show cell cycle arrest, induction of apoptosis and reduced invasive and migratory capabilities. Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. Genistein inhibited the expression of miR-21 in A-498 cells and in the tumors formed after injecting genistein treated A-498 cells in nude mice besides inhibiting tumor formation.
  
  
  CONCLUSIONS
  The current study shows a clear correlation between miR-21 expression and clinical characteristics of renal cancer. Thus we believe that miR-21 can be used as a tumor marker and its inhibition may prove to be useful in controlling cancers with up-regulated miR-21.
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mohd Saif
authors.initials: MS
authors.lastname: Zaman
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Sobha
authors.initials: S
authors.lastname: Thamminana
authors.forename: Sharonjot
authors.initials: S
authors.lastname: Saini
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Inik
authors.initials: I
authors.lastname: Chang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.forename: Kamaldeep
authors.initials: K
authors.lastname: Singh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000818:Animals; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D015996:Survival Rate; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D019833:Genistein