TCF7 is suppressed by the androgen receptor via microRNA-1-mediated downregulation and is involved in the development of resistance to androgen deprivation in prostate cancer

Mk, Siu; Wy, Chen; Hy, Ts'ai; Hy, Chen; Jj, Yin; Cl, Chen; Tsai, Yu-Chen; Yn, Liu

doi:10.1038/pcan.2017.2

Cited by 25 publications

(20 citation statements)

References 42 publications

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“…Many TCF variants with distinct properties are produced by the alternative splicing and promoter usage [4,20], resulting in distinct and sometimes redundant functions of TCF genes. In the TCF family, the upregulation of TCF7 was observed in many types of cancers, such as prostate cancer [8], adrenocortical tumor [21], pancreatic cancer [22], renal cancer [23], and breast cancer [24]. In our study, we demonstrated that TCF7 was significantly associated with positive metastasis of GC, perhaps because TCF7 promotes the invasion-involved Wnt target gene in GC cells.…”

Section: Discussionmentioning

confidence: 51%

“…As a transcriptional activator, much evidence demonstrates that overexpression of TCF7 promotes progression or correlates with poor prognosis in several types of cancers. Moreover, the downregulation of TCF7 by some miRNAs can suppress tumor progression or carcinogenesis [6–8]. Ectopic activation of Wnt signaling is critical in progression of gastric cancer [9], but the expression and clinical significance in gastric cancer has never been explored.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Significance of Transcription Factor 7 (TCF7) as a Prognostic Factor in Gastric Cancer

Liu

Tian

et al. 2019

Med Sci Monit

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Background Transcription factor 7 (TCF7) plays an essential role in Wnt signaling by interacting with β-catenin. Emerging evidence demonstrates that overexpression of TCF7 promotes progression or correlates with poor progression in several types of cancers, but the functions of TCF7 in gastric cancer (GC) have not been revealed. Material/Methods A total of 168 patients with GC who underwent radical surgeries were collected and regarded as the test cohort. The expression of TCF7 in the 168 patients was detected with immunohistochemistry. Moreover, the mRNA levels of TCF7 in 11 pairs of GC and adjacent tissues were detected with quantitative real-time PCR (qRT-PCR). The correlations between TCF7 and the clinicopathological factors were evaluated with the chi-square test, and the prognostic value of TCF7 in GC was investigated with univariate analysis and multivariate analysis. Results The mRNA levels of TCF7 in GC tissues were significantly higher than in corresponding tumor adjacent tissues. The patients of low TCF7 expression and high TCF7 expression accounted for 76.79% (129/168) and 23.21% (39/168), respectively. In our experiments, TCF7 was significantly associated with positive lymphatic invasion ( P =0.022) and metastasis ( P <0.001). The high expression of TCF7 was correlated with low survival rates ( P =0.012) and was confirmed as an independent prognostic factor (HR=1.92, 95%CI =1.06–3.47, P=0.031) of GC in multivariate analysis. Conclusions TCF7 expression is correlated with metastasis and is an independent prognostic factor of GC. TCF7 detection of GC could help stratify the patients with high risk and guide precise treatment.

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Transcription Factor 7 (TCF7) as a Prognostic Factor in Gastric Cancer

Liu

Tian

et al. 2019

Med Sci Monit

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“…44,45 Tcf7 is one of the members of the Tcf/lef family. Abnormally expressed high Tcf7 was found in many types of cancer, such as prostate cancer 46 and renal cell carcinoma. 47 It plays an important role in cancer on Wnt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>Combination of Inositol Hexaphosphate and Inositol Inhibits Liver Metastasis of Colorectal Cancer in Mice Through the Wnt/β-Catenin Pathway</p>

Liu¹,

Liu²,

Chen³

et al. 2020

OTT

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Introduction: Colorectal cancer, one of the most common tumors, is mainly fatal because of the occurrence of liver metastasis. Inositol hexaphosphate (IP6) and inositol (INS) were found, both, in vitro and in vivo to play an anti-tumor effect, whereas the combination of IP6 and INS was more effective than IP6 or INS alone. Materials and Methods: The inhibitory effects of IP6, INS and the combination of IP6 +INS on tumor progression and liver metastasis of colorectal cancer were investigated in an orthotopic transplantation model of colorectal cancer. The tumor-bearing mice were selected by in vivo bioluminescence imaging and were treated with IP6, INS, and IP6 combined with INS, respectively. All mice were sacrificed after 6 weeks of treatment. The cancer development and metastasis were compared among the groups. The expression of genes related to the Wnt/β-catenin in the model was analyzed. Results: The results demonstrated that liver metastasis was inhibited after treatment with IP6, INS, and IP6+INS. Compared to that of the M_G, survival period was extended, and tumor weight was lowered in IP6_G, INS_G, and IP6+INS_G. Besides, the liver metastatic area of mice in IP6+INS_G was relatively smaller than that in M_G, IP6_G, or INS_G. The results of RNA-seq analysis showed that the expressions of Wnt10b, Tcf7, and c-Myc were significantly downregulated in IP6+INS_G compared to that in M_G (P<0.05). Results of real-time PCR and Western blot showed that mRNA and protein expressions of β-catenin, Wnt10b, Tcf7, and c-Myc were significantly lower in IP6+INS_G compared to that in M_G (P<0.05). Discussion: IP6+INS was more effective in inhibiting liver metastasis of colorectal cancer than IP6 or INS alone. The better inhibition effect may be accomplished through regulating the mutation of Wnt/β-catenin signaling pathway by inhibiting Wnt10b, Tcf7, β-catenin, and c-Myc from abnormally high expression.

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“…Interestingly, the miR-1-2 promoter is also targeted by ‘Kruppel like factor 4’ (Klf4), which expression itself is induced by the AR [95]. Additionally, androgen-induced miR-1 downregulates TCF7 in prostate cancer cell lines and therefore negatively impacts the Wnt signaling pathway [96]. Another target gene of miR-1, in the context of the transition of PCa from androgen-sensitive to castration-resistant, is ZBTB46 [97].…”

Section: Androgen-regulated Micrornas (Andromirs)mentioning

confidence: 99%

Androgen-Regulated microRNAs (AndroMiRs) as Novel Players in Adipogenesis

Jansen

Greither

Behre

2019

IJMS

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The development, homeostasis, or increase of the adipose tissue is driven by the induction of the adipogenic differentiation (adipogenesis) of undifferentiated mesenchymal stem cells (MSCs). Adipogenesis can be inhibited by androgen stimulation of these MSCs resulting in the transcription initiation or repression of androgen receptor (AR) regulated genes. AR not only regulates the transcription of protein-coding genes but also the transcription of several non-coding microRNAs involved in the posttranscriptional gene regulation (herein designated as AndroMiRs). As microRNAs are largely involved in differentiation processes such as adipogenesis, the involvement of AndroMiRs in the androgen-mediated inhibition of adipogenesis is likely, however, not yet intensively studied. In this review, existing knowledge about adipogenesis-related microRNAs and AndroMiRs is summarized, and putative cross-links are drawn, which are still prone to experimental validation.

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TCF7 is suppressed by the androgen receptor via microRNA-1-mediated downregulation and is involved in the development of resistance to androgen deprivation in prostate cancer

Abstract: We demonstrated that the AR-miR-1 axis negatively regulates the novel oncogenic factor, TCF7. Dysregulation of TCF7 promoted a survival advantage and resistance to androgen deprivation, suggesting its therapeutic potential for castration-resistant prostate cancer.

Cited by 25 publications

References 42 publications

Clinical Significance of Transcription Factor 7 (TCF7) as a Prognostic Factor in Gastric Cancer

Clinical Significance of Transcription Factor 7 (TCF7) as a Prognostic Factor in Gastric Cancer

<p>Combination of Inositol Hexaphosphate and Inositol Inhibits Liver Metastasis of Colorectal Cancer in Mice Through the Wnt/β-Catenin Pathway</p>

Androgen-Regulated microRNAs (AndroMiRs) as Novel Players in Adipogenesis

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