Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network

Abstract

High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR-149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4–2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development.

miRNA-346 promotes proliferation, migration and invasion in liver cancer

“…Increasing data findings have indicated miRNAs to be critical regulators of cancer-related processes, but it is still unknown the molecu lar mechanisms by which miRNAs modulate the behavior of cancer cells (26,27). miR-346 has been reported as an oncomir because it facilitates cell growth and metastasis in various human cancers (16)(17)(18)(19)(20)(21). This is the first study that indicates that ectopically expressed miR-346 can promote migration, proliferation, and invasion of liver cancer cells.…”

“…Emerging evidence suggests that the abnormal expression of miRNAs is involved in the invasion and metastasis, during the progression of various human cancers (14,15). miR-346 has been reported as an oncomir in various human cancers, including cutaneous squamous cell carcinoma (16), cervical cancer (17), prostate cancer (18), nasopharyngeal carcinoma (19), lung cancer (20) and breast cancer (21).…”

Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy

“…This event plays an important role in promoting cell migration and the development of metastasis. Several miRNAs, such as the miRNA-200 family, miRNA132/212, miRNA-205, and miRNA-203 promote the epithelial state and have been shown to inhibit the EMT [50,51,54,55] .…”

Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach

“…According to the statistical evidences described in our previous work, miRNAs with larger NOD and TFP values were more likely to be candidate biomarkers and represented biomarker miRNAs that had strong abilities to regulate genes independently and, meanwhile, regulate more TF genes. The application of biomarker discovery for prostate cancer [23, 25], sepsis [26], clear cell renal cell carcinoma [27], and pediatric acute myeloid leukemia [24] demonstrated its great predictive power.…”