MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway

I. Shan Hsieh, Kung Chao Chang, Yao Tsung Tsai, Jhen Yu Ke, Pei Jung Lu, Kuen Haur Lee, Shauh Der Yeh, Tse Ming Hong, Yuh Ling Chen

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Abstract

Prostate cancer (PCa) is a leading cause of mortality and morbidity in men worldwide, and emerging evidence suggests that the CD44high prostate tumor-initiating cells (TICs) are associated with its poor prognosis. Although microRNAs are frequently dysregulated in human cancers, the influence of microRNAs on PCa malignancy and whether targeting TIC-associated microRNAs inhibit PCa progression remain unclear. In this study, we found that miR-320 is significantly downregulated in PCa. Overexpression of miR-320 in PCa cells decreases PCa tumorigenesis in vitro and in vivo. Global gene expression profiling of miR-320-overexpressing PCa cells reveals that downstream target genes of Wnt/β-catenin pathway and cancer stem cell markers are significantly decreased. MicroRNA-320 inhibits β-catenin expression by targeting the 3'-untranslated region of β-catenin mRNA. The reduction of miR-320 associated with increased β-catenin was also found in CD44high subpopulation of prostate cancer cells and clinical PCa specimens. Interestingly, knockdown of miR-320 significantly increases the cancer stem-like properties, such as tumorsphere formation, chemoresistance and tumorigenic abilities, although enriching the population of stem-like TICs among PCa cells. Furthermore, increased miR-320 expression in prostate stem-like TICs significantly suppresses stem cell-like properties of PCa cells. These results support that miR-320 is a key negative regulator in prostate TICs, and suggest developing miR-320 as a novel therapeutic agent may offer benefits for PCa treatment.

Original languageEnglish
Pages (from-to)530-538
Number of pages9
JournalCarcinogenesis
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Wnt Signaling Pathway
MicroRNAs
Prostatic Neoplasms
Stem Cells
Down-Regulation
Neoplastic Stem Cells
Catenins
Prostate
Neoplasms
3' Untranslated Regions
Gene Expression Profiling
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research

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MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. / Hsieh, I. Shan; Chang, Kung Chao; Tsai, Yao Tsung; Ke, Jhen Yu; Lu, Pei Jung; Lee, Kuen Haur; Yeh, Shauh Der; Hong, Tse Ming; Chen, Yuh Ling.

In: Carcinogenesis, Vol. 34, No. 3, 03.2013, p. 530-538.

Research output: Contribution to journalArticle

Hsieh, I. Shan ; Chang, Kung Chao ; Tsai, Yao Tsung ; Ke, Jhen Yu ; Lu, Pei Jung ; Lee, Kuen Haur ; Yeh, Shauh Der ; Hong, Tse Ming ; Chen, Yuh Ling. / MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway. In: Carcinogenesis. 2013 ; Vol. 34, No. 3. pp. 530-538.
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