Anticancer effect of icaritin on prostate cancer via regulating miR‐381‐3p and its target gene UBE2C

Hu, Jimeng; Wu, Xiaoqing; Yang, Chen; Rashid, Khalid; Ma, Chenkai; Hu, Mengbo; Ding, Qiang; Jiang, Haowen

doi:10.1002/cam4.2630

Cited by 43 publications

(44 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, miR-381-3p overexpression promotes cancer cell proliferation in glioblastoma cells and osteosarcoma cells by targeting the brain relative specific expression gene LRRC4 (Tang et al, 2011;Li et al, 2016). On the contrary, miR-381-3p functions as a tumor suppressor gene in rectal cancer and prostate cancer through suppression of UBE2C (Zhang et al, 2018;Hu et al, 2019). Through a cellbased screening for miRNAs regulating apoptosis, we found that miR-381-3p negatively regulates TNF-induced apoptosis in multiple human cancer cell lines.…”

Section: Discussionmentioning

confidence: 96%

MicroRNA-381-3p Functions as a Dual Suppressor of Apoptosis and Necroptosis and Promotes Proliferation of Renal Cancer Cells

Zhao

Zhou

Ran

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) is the most common type of kidney cancer. It has a poor prognosis, with approximately 20-30% of patients developing recurrent and/or metastatic diseases that is relatively high resistant to conventional therapy. Resisting cell death is a hallmark of cancer cells. Apoptosis is a form of programmed cell death mediated by the activation of caspases. Necroptosis is a form of regulated necrosis that relies on the activation of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL), the substrate of RIPK3. Cancer cells often display apoptosis resistance via upregulation of anti-apoptotic genes and defective necroptosis due to the epigenetic silence of Ripk3. MicroRNAs (miRNAs) are non-coding small RNAs that are involved in numerous biological processes including cell proliferation, differentiation and death. In this study, we screened a set of ∼120 miRNAs for apoptosis-regulating miRNAs and identified miR-381-3p as a suppressor of TNFinduced apoptosis in various cancer cells. Ectopic expression of miR-381-3p inhibits the activation of caspase-8 and caspase-3. The expression level of miR-381-3p inversely correlates with the sensitivity of cancer cells to TNF-induced apoptosis. Moreover, we found that overexpression of miR-381-3p blocks TNF-induced necroptosis by inhibiting the activation of RIPK3 and MLKL. Of note, Kaplan-Meier Plotter analysis demonstrates that papillary RCC patients with high miR-381-3p expression have a lower overall survival than those with low expression level of miR-381-3p. Importantly, miR-381-3p overexpression promotes colony formation in human renal cancer cells. Thus, miR-381-3p acts as an oncogenic miRNA that counteracts both apoptotic and necroptotic signaling pathways. Our findings highlight miR-381-3p as a biomarker for predicting sensitivity to apoptosis and necroptosis, and as a possible therapeutic target for RCC.

show abstract

Section: Discussionmentioning

confidence: 96%

MicroRNA-381-3p Functions as a Dual Suppressor of Apoptosis and Necroptosis and Promotes Proliferation of Renal Cancer Cells

Zhao

Zhou

Ran

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…In addition, recent studies have shown that miR-381 has a very important role in tumor oncogenesis, development, metastasis and chemical resistance. For example, miR-381 inhibits the proliferation and invasion of prostate cancer cells via the regulation of UBE2C [41]; miR-381 inhibits lung adenocarcinoma progression by directly targeting LMO3 through the regulation of the PI3K/Akt signaling pathway and EMT [42]; up-regulation of miR-381 inhibits the NAD + salvage pathway and promotes apoptosis in breast cancer cells [43]; miR-381 overcomes cisplatin resistance in breast cancer cells by targeting MDR1 [44]. In line with these findings, metformin upregulated the level of miR-381 to inhibit NSCLC tumor growth and metastasis in our study.…”

Section: Discussionmentioning

confidence: 99%

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

Jin

Guo

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background: Recent evidence indicates that metformin inhibits mammalian cancer growth and metastasis through the regulation of microRNAs. Metformin regulates miR-381 stability, which plays a vital role in tumor progression. Moreover, increased YAP expression and activity induce non-small cell lung cancer (NSCLC) tumor growth and metastasis. However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown. Methods: Levels of RNA and protein were analyzed using qPCR, western blotting and immunofluorescence staining. Cellular proliferation was detected using a CCK8 assay. Cell migration and invasion were analyzed using wound healing and transwell assays. Promoter activity and transcription were investigated using the luciferase reporter assay. Chromatin immunoprecipitation was used to detect the binding of YAP to the promoter of Snail. The interaction between miR-381 and the 3′UTR of YAP mRNA was analyzed using the MS2 expression system and co-immunoprecipitation with biotin. Results: We observed that miR-381 expression is negatively correlated with YAP expression and plays an opposite role to YAP in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. The miR-381 function as a tumor suppressor was significantly downregulated in lung cancer tissue specimens and cell lines, which decreased the expression of its direct target YAP. In addition, metformin decreased cell growth, migration, invasion, and EMT via up-regulation of miR-381. Moreover, YAP, which functions as a co-transcription factor, enhanced NSCLC progression and metastasis by upregulation of Snail. Snail knockdown downregulated the mesenchymal marker vimentin and upregulated the epithelial marker E-cadherin in lung cancer cells. Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT. Conclusions: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis. Thus, we believe that the miR-381-YAP-Snail signal axis may be a suitable diagnostic marker and a potential therapeutic target for lung cancer.

show abstract

“…Recent studies revealed the anti-inflammatory and anti-survival activities of ICT in various cancer types including PCa 15 , 16 , 18 - 20 . It is established that HFD-induced obesity is a well-known risk factor for the development of various diseases, including cancer, through regulatory mechanisms 2 , 21 .…”

Section: Discussionmentioning

confidence: 99%

Icaritin reduces prostate cancer progression via inhibiting high-fat diet-induced serum adipokine in TRAMP mice model

Long

Yang

et al. 2020

J. Cancer

Self Cite

View full text Add to dashboard Cite

Objective: Obesity resulting from high-fat diets has a close relationship with the morbidity and mortality associated with Prostate cancer (PCa) in males. The anti-cancer role of Icaritin (ICT, a traditional Chinese herbal medicine) has been reported in several types of cancer including PCa. Adipokines are novel adipocyte-specific secretory protein, which plays a key role in the development of various diseases including obesity, diabetes, atherosclerosis, and cancer. However, the function of ICT and the molecular mechanisms underlying its role in PCa regression through modulation of adipokines have not been studied. Here, we assessed the anti-cancer properties of ICT under the influence of human epidermal growth factor receptor type 2 (HER2) pathway modulating adipokines in obese PCa models. Materials and Methods: In this study, we used transgenic adenocarcinoma of mouse prostate (TRAMP), a well-established animal model for the study of PCa pathogenesis. All the animals were fed on a high-fat diet (HFD with 40% fat) and divided into two groups, one received ICT solution of 30 mg/kg body bwt (i.p) while the other group served as control without any ICT treatment. The mortality rate, tumor formation and fat ratio were assessed by histopathological and magnetic resonance analysis at different time points of 20 th , 24 th and 28 th weeks. The protein expression of HER2 and serum levels of adipokines were measured using western blotting, IHC and multiplex immunoassays. The PCa grade in 12 TRAMP mice were longitudinally evaluated to visualize PCa development and progression upon post-surgery using PET/CT scanning. Results: We observed that ICT treatment significantly reduces the total mortality rate of TRAMP mice (p = 0.045) and the percentage of prostate intraepithelial neoplasia (PIN) or PCa (p = 0.029). Interestingly, significantly decreased levels of leptin (p = 0.006 @20 th wk) and the elevated levels of adiponectin (p = 0.030 @20 th wk) were observed in different subgroups upon ICT treatment in a time-dependent manner. In addition, a decrease level of HER2 (p = 0.032 @28 th wk) and an elevated level of PEA3 (p = 0.014 @28 th wk) were also detected in ICT treated group. The PET/CT-based imaging showed that ICT vs non-ICT treated mice had different standard uptake value and metastasis. Discussion and Conclusion: Our results showed potent anti-cancer properties of ICT through the modulation of adipokine secretion may alter the expression and activation of HER2 pathway as an alternative mechanism to prevent PCa progression. Altogether, our findings indicate that ICT could be a promising cancer preventive agent with the potential to target and eradicate tumor cells in obese PCa patients.

show abstract

Anticancer effect of icaritin on prostate cancer via regulating miR‐381‐3p and its target gene UBE2C

Cited by 43 publications

References 43 publications

MicroRNA-381-3p Functions as a Dual Suppressor of Apoptosis and Necroptosis and Promotes Proliferation of Renal Cancer Cells

MicroRNA-381-3p Functions as a Dual Suppressor of Apoptosis and Necroptosis and Promotes Proliferation of Renal Cancer Cells

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

Icaritin reduces prostate cancer progression via inhibiting high-fat diet-induced serum adipokine in TRAMP mice model

Contact Info

Product

Resources

About