1622 LIN28/MIR-LET-7C AXIS CONTROLS THE GROWTH AND TUMORIGENICITY OF PROSTATE CANCER CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111622 LIN28/MIR-LET-7C AXIS CONTROLS THE GROWTH AND TUMORIGENICITY OF PROSTATE CANCER CELLS Nagalakshmi Nadiminty, Ramakumar Tummala, Jaeyeon Chun, Wei Lou, Xubao Shi, Ralph deVere White, and Allen Gao Nagalakshmi NadimintyNagalakshmi Nadiminty Sacramento, CA More articles by this author , Ramakumar TummalaRamakumar Tummala Sacramento, CA More articles by this author , Jaeyeon ChunJaeyeon Chun Sacramento, CA More articles by this author , Wei LouWei Lou Sacramento, CA More articles by this author , Xubao ShiXubao Shi Sacramento, CA More articles by this author , Ralph deVere WhiteRalph deVere White Sacramento, CA More articles by this author , and Allen GaoAllen Gao Sacramento, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1730AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MicroRNAs (miRNA) are small ∼22 nt non-coding RNAs that regulate gene expression by binding to and inducing degradation of target mRNAs. Deregulated expression of several miRNAs has been found in prostate cancer cells. Let-7 is an evolutionarily conserved family of miRNAs that have been shown to regulate expression of several oncogenes like HMGA2, RAS and Myc. Expression of members of the let-7 family has been shown to be downregulated in many human cancers including lung, breast, ovarian and prostate. In this study, we examined the relative expression levels of let-7c and its master regulator, Lin28 in prostate cancer cells and clinical specimens. We also examined the role of the let-7/Lin28 axis in controlling proliferation in prostate cancer cells. METHODS Expression levels of Let-7c and Lin28 in prostate cancer cells and clinical specimens were measured by real-time qRT-PCR, Northern and Western blotting. Prostate cancer cell lines with stable expression of let-7c or Lin28 were generated and their growth characteristics, clonogenic ability and colony forming abilities in soft agar were examined. Expression of let-7c was downregulated in LNCaP cells using antisense oligonucleotides and effects on growth were examined. Lentiviruses containing let-7c were injected into tumors generated by implantation of prostate cancer cells in nude mice and tumor volumes were measured. RESULTS Expression levels of let-7c were found to be downregulated in castration-resistant prostate cancer cells and clinical specimens. These levels were found to be inversely correlated to expression levels of Lin28. Overexpression of let-7c reduced prostate cancer cell growth, clonogenic ability and ability to form colonies in soft agar, while downregulation of let-7c resulted in increased cell growth. Conversely, overexpression of Lin28 enhanced prostate cancer cell growth and clonogenic ability. In addition, intratumoral injection of lentiviruses containing let-7c reduced tumor volumes significantly in vivo in nude mice compared to control viruses. CONCLUSIONS Levels of miR-let-7c are reduced in CRPC compared to androgen-dependent prostate cancer. Levels of Lin28, which regulates processing of let-7c into its mature form, are elevated in CRPC. Overexpression of let-7c reduces prostate cancer cell growth and tumorigenic ability. These results suggest that miR-let-7c is a tumor suppressor and may be developed as a therapeutic agent against CRPC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e650 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nagalakshmi Nadiminty Sacramento, CA More articles by this author Ramakumar Tummala Sacramento, CA More articles by this author Jaeyeon Chun Sacramento, CA More articles by this author Wei Lou Sacramento, CA More articles by this author Xubao Shi Sacramento, CA More articles by this author Ralph deVere White Sacramento, CA More articles by this author Allen Gao Sacramento, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...