title: Inhibition of PTEN gene expression by oncogenic miR-23b-3p in renal cancer.
abstract: BACKGROUND
  miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC) has not been reported.
  
  
  RESULTS
  We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR. The expression level of miR-23b-3p was correlated with the 5 year survival rate of renal cancer patients. In 15 cases (52%), miR-23b-3p expression was found to be high. All patients with moderate to low miR-23b-3p expression survived 5 years, while those with high miR-23b-3p expression, only 50% survived. After knocking down miRNA-23b-3p expression in RCC cell lines, there was an induction of apoptosis and reduced invasive capabilities. MiR-23b-3p was shown to directly target PTEN gene through 3'UTR reporter assays. Inhibition of miR-23b-3p induces PTEN gene expression with a concomitant reduction in PI3-kinase, total Akt and IL-32. Immunohistochemistry showed the lack of PTEN protein expression in cancerous regions of tissue samples where the expression of miR-23b-3p was high. We studied the in vitro effects of the dietary chemo preventive agent genistein on miR-23b-3p expression and found that it inhibited expression of miR-23b-3p in RCC cell lines.
  
  
  CONCLUSIONS
  The current study shows that miR-23b-3p is an oncogenic miRNA and inhibits PTEN tumor suppressor gene in RCC. Therefore, inhibition of miR-23b-3p may be a useful therapeutic target for the treatment of renal cell carcinoma.
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: Sobha
authors.initials: S
authors.lastname: Thamminana
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Inik
authors.initials: I
authors.lastname: Chang
authors.forename: Sumit
authors.initials: S
authors.lastname: Arora
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.forename: Kamaldeep
authors.initials: K
authors.lastname: Singh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D019833:Genistein / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D019833:Genistein; D051059:PTEN Phosphohydrolase