Registered report: the microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44

Abstract

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altimetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ by Liu and colleagues published in Nature Medicine in 2011 (Liu et al., 2011). Liu and colleagues first demonstrated that miR-34a levels were reduced in CD44+ prostate cancer cells (Figure 1B). They then showed that xenograft tumors from cells expressing exogenous miR-34a were smaller in size than control tumors (Supplemental Figure 5C). Tumors with exogenous miR-34a showed reduced levels of CD44 expression (Figure 4A), and mutation of two putative miR-34a binding sites in the CD33 3′ UTR partially abrogated signal repression in a luciferase assay (Figure 4D). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.DOI: http://dx.doi.org/10.7554/eLife.06434.001

Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression

“…Members of miR-34 family (-a, -b, -c) were reported to suppress tumorigenesis by several mechanisms including regulation of cell cycle, EMT and/or metastasis [ 77 , 78 , 79 , 80 , 81 ]. In cancer, p53, a major tumor suppressive transcription factor, induce miR-34 family [ 82 ].…”

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a ″Watch-and-Wait″� Approach to Cancer

“…Such miRNAs specific blockade of miRNAs signaling can serve as cancer subclonal switching board management [80], effectively keeping certain cancer subclones in the sleep stage (dormant state) so that we can exercise “watch-and-wait” approach to cancer. This concept is directly supported by Liu and colleagues’ report showing that while miR-34a, a p53 target, underexpressed in CD44+ prostate cancer cells, enforced expression of miR-34a in CD44+ prostate cancer cells inhibits clonogenic expansion, tumor regeneration, and metastasis [81, 82]. Chang and colleagues show that by acting as a tumor-suppressor, microRNA-7 (miR-7)-mediated KLF4/PI3K/Akt/p21 pathway is critical for prostate cancer stem-like cells (PCSCs) stemness - A negative correlation between miR-7 expression and prostate tumor progression implicates its potential application for prostate cancer therapy [83].…”

The roles of microRNAs in the progression of castration-resistant prostate cancer

“…50 miR-34a has been shown to be downregulated in CD44+ PCa cells, and these cells have increased inhibition of clonogenic growth, metastatic behavior and tumor regenerator. 57,58 The tumor suppressor p53 induces transcription of miR-34a, which is known to have strong anti-tumor effects. The let-7 family also appears to have a key role in the recurrence and progression of PCa by regulating CSCs.…”