FOXA1 in prostate cancer / 亚洲男科学杂志(英文版)

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

MicroRNA-30a inhibits proliferation of hepatocellular carcinoma cells via targeted regulation of forkhead-box protein A1 / 中华肝脏病杂志

Objective@#To investigate the expression of microRNA-30a (miR-30a) in hepatocellular carcinoma (HCC) and related molecular mechanisms in regulating HCC cell proliferation.@*Methods@#A total of 30 pairs of HCC and adjacent tissue samples were collected, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of forkhead-box protein A1 (FOXA1). Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of HCC cells, luciferase reporter gene assay was performed to verify the target relationship between miR-30a and FOXA1, and MTT assay and Western blot were used to measure the proliferation of HepG2 cells and the protein expression of FOXA1 after miR-30a transfection. The t-test was used for comparison of data between two groups, and a one-way analysis of variance was used for comparison of data between multiple groups. P < 0.05 was considered statistically significant.@*Results@#HCC tissue had significantly lower relative expression of miR-30a than adjacent tissue (1.049 ± 0.380 vs 1.982 ± 1.013, t = 3.985, P < 0.001). At 72 hours after miR-30a overexpression, there was a significant difference in the proliferative capacity of HepG2 cells between the blank control group, the miR-30a-NC group, and the miR-30a group (0.821 ± 0.006 vs 0.816 ± 0.013 vs 0.546 ± 0.020, F = 3.396, P < 0.05), suggesting that miR-30a overexpression significantly inhibited the proliferation of HepG2 cells. FOXA1 was a target gene of miR-30a and its protein expression was negatively regulated by miR-30a, and there was a significant difference in luciferase activity between wild-type and mutant FOXA1-3’UTR vectors (1.221 ± 0.024 vs 2.658 ± 0.031, F = 6.737, P < 0.05). In HepG2 cells, miR-30a overexpression significantly inhibited the protein expression of FOXA1, and there was a significant difference in the relative expression of FOXA1 between the blank control group, the miR-30a-NC group, and the miR-30a group (1.019 ± 0.016 vs 1.022 ± 0.017 vs 0.227 ± 0.021, F = 45.43, P < 0.05). Upregulating the protein expression of FOXA1 reversed the inhibitory effect of miR-30a on the proliferation of HepG2 cells, and there was a significant difference in the proliferative capacity of HepG2 cells between the miR-30a group and the miR-30a+FOXA1 group (0.524 ± 0.023 vs 0.843 ± 0.019, t = 2.507, P < 0.05).@*Conclusion@#MiR-30a exerts its inhibitory effect on the proliferation of HCC cells by negatively regulating the expression of FOXA1.