title: Regulation of SRC kinases by microRNA-3607 located in a frequently deleted locus in prostate cancer.
abstract: Genomic studies suggest that deletions at chromosome (chr) 5q region (particularly chr5q14-q23) are frequent in prostate cancer, implicating this region in prostate carcinogenesis. However, the genes within this region are largely unknown. Here, we report for the first time the widespread attenuation of miR-3607, an miRNA gene located at chr5q14 region, in prostate cancer. Expression analyses of miR-3607 in a clinical cohort of prostate cancer specimens showed that miR-3607 is significantly attenuated and low miR-3607 expression is correlated with tumor progression and poor survival outcome in prostate cancer. Our analyses suggest that miR-3607 expression may be a clinically significant parameter with an associated diagnostic potential. We examined the functional significance of miR-3607 in prostate cancer cell lines and found that miR-3607 overexpression led to significantly decreased proliferation, apoptosis induction, and decreased invasiveness. Furthermore, our results suggest that miR-3607 directly represses oncogenic SRC family kinases LYN and SRC in prostate cancer. In view of our results, we propose that miR-3607 plays a tumor-suppressive role in prostate cancer by regulating SRC kinases that in turn regulates prostate carcinogenesis. To our knowledge, this is the first report that: (i) identifies a novel role for miR-3607 located in a frequently deleted region of prostate cancer and (ii) defines novel miRNA-mediated regulation of SRC kinases in prostate cancer. Because SRC kinases play a central role in prostate cancer progression and metastasis and are attractive targets, this study has potential implications in the design of better therapeutic modalities for prostate cancer management.
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California SainiS@urology.ucsf.edu.
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Sumit
authors.initials: S
authors.lastname: Arora
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
authors.affiliation: Authors' Affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California.
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
mesh_terms: D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D019061:src-Family Kinases