The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44 (Nat Med, 2011, doi:10.1038/nm2284)

報告日期: 2011/04/22
報告時間: 16:00/16:50
報告學生: 陳韋靜
講評老師: 吳梨華

Full Text:

 The microRNA miR-34a inhibits prostate
cancer stem cells and metastasis by directly
repressing CD44  
Nat Med. 2011 Feb;17(2):211-5. Epub 2011 Jan 16..
Speaker : 陳韋靜 
Commentator :吳梨華 老師
Date: 2011.4.22
Room: 602
   Cancer stem cells (CSCs) are a rare subpopulation of cancer cells. They are tumorigenic, meanwhile capable of self-renewal and forming differentiated progenies. Cancer stem cells are believed to be more resistant to escape the chemotherapy. Therefore, it is essential to elucidate the signaling and regulatory mechanisms that are unique to CSCs in order to design CSC-specific therapies. MicroRNAs (miRNAs)regulate differentiation and can function as either tumor suppressors or oncogenes to regulate tumor development and prognosis. In addition, miRNAs regulate both normal stem cells and CSCs. CD44 was used as a marker to isolate CSCs from tumor, including breast cancer, liver cancer, pancreas cancer and prostate cancer. However, whether miRNAs regulate CD44+ prostate cancer cells remains unclear. The author purified the CD44+ and CD44- cell from the xenograft and primary tumors and then assayed the miR-34a expression. The data showed that the miR-34a was underexpressed in the CD44+ cell. Besides, the miR-34a inhibited the prostate cancer stem cell property, including the sphere assay and holoclone assay. Furthermore, the miR-34a inhibited the tumor regeneration and metastasis ability of the CD44+ prostate cancer cells. In order to determine whether CD44 is a functionally important target of
miR-34a in the context of prostate cancer development, the author reduced the CD44 expression and found that knockdown of CD44 inhibited the tumor development. The author further found that the miR-34a binding site is existed in the 3’UTR of the CD44 mRNA. Therefore, the author propose that miR-34a is a key negative regulator of CD44+ prostate cancer cells and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against prostate CSCs.
Patrawala, L. et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25,1696–1708 (2006).