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.

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Prostate cancer is a heritable and clinically heterogeneous cancer. Both long non‐coding RNAs (lncRNAs) and microRNAs (miRs) have been implicated in the pathogenesis and development of prostate cancer. Analysis of microarray data indicated that the lncRNA LINC01207 was differentially expressed in prostate cancer. In silico analysis predicted the interaction between LINC01207 and miR‐1972 as well as the interaction between miR‐1972 and the mRNAs LIM and SH3 protein 1 (LASP1). Thus, we explored the role of LINC01207 and miR‐1972 in the growth and progression of prostate cancer. Quantitative real‐time polymerase chain reaction revealed that LINC01207 and LASP1 were highly expressed in prostate cancer, while miR‐1972 expression was lower. The interaction among LINC01207, miR‐1972, and LASP1 was confirmed by RNA‐fluorescence in situ hybridization, RNA immunoprecipitation, and dual luciferase reporter assay, which verified that LINC01207 could bind to miR‐1972 and downregulate miR‐1972, and miR‐1972 targeted LASP1 and negatively regulated its expression. Both in vitro and in vivo experiments found that silencing LINC01207 inhibited cell proliferation, migration, invasion and tumor formation and enhanced apoptosis in prostate cancer cells, suggesting that LINC01207 functioned as a tumor promoter in prostate cancer and that it may represent a novel therapeutic target.

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Castration-resistant prostate cancer (CRPC) is a heterogeneous disease with a high mortality rate. MicroRNA let-7b has been documented to act as a tumor suppressor in various cancers. The present study intends to explore how let-7b affects CRPC by influencing the Ras/Rho signaling pathway. The expression of neuroblastoma RAS viral oncogene homolog (NRAS) and let-7b in CRPC tissues and cells was determined. The binding relationship between let-7b and NRAS was predicted by the Targetscan website and verified by the dual luciferase reporter gene assay. Gain-of-function and loss-of-function approaches were used to investigate the relationship among let-7b, NRAS, and Ras/Rho signaling pathway as well as their effects on the proliferation, invasion, and apoptosis of CRPC cells. The tumor formation ability of nude mice was tested in vivo. Poorly expressed Let-7b and highly expressed NRAS were presented in CRPC tissues and androgen-independent cell line C4-2. NRAS was verified as a target gene of let-7b. Overexpression of let-7b or silencing of NRAS repressed C4-2 cell proliferation and invasion in vitro and tumor growth in vivo as well as induced C4-2 cell apoptosis in vitro through the blockage of the Ras/Rho signaling pathway. Let-7b overexpression or NRAS silencing reduced matrix metalloproteinase-2, matrix metalloproteinase-9, Bcl-2, cyclinD1, and CyclinB expression, but elevated Caspase3 expression in vivo and in vitro. Taken together, in CRPC, let-7b blocks the Ras/Rho signaling pathway by inhibiting NRAS expression, thereby inhibiting cell proliferation and invasion, and promoting cell apoptosis. Thus, let-7b targeting NRAS may be a potential therapeutic target for the repression of CRPC.Prostate cancer is a kind of noncutaneous cancer with the highest morbidity and the second highest mortality among men. 1 In recent years, advanced and metastatic prostate cancer have become a heavy burden that cannot be solved in short term in the healthcare system. 2 For metastatic prostate cancer, patients can only receive temporary disease control measures by blockading or castrating androgen. 3 Usually, prostate cancer may develop into a lethal form of castration-resistant prostate cancer (CRPC) within 2-3 years as the majority of patients resist to the treatment. 4 CRPC is historically considered as a kind of chemoresistant tumor with a palliative treatment only lasting 1-2 years. 5 It is a major challenge in the treatment of CRPC for lacking easily available and reliable biomarkers. 6 For the same, we conducted a series of experiments in the present study to explore new targets for CRPC treatment.Let-7b belongs to the microRNA let-7 family and usually acts as a tumor suppressor in different types of

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