MiR-644a Disrupts Oncogenic Transformation and Warburg Effect by Direct Modulation of Multiple Genes of Tumor-Promoting Pathways

Prostate cancer is the second most common malignancy in men and androgen deprivation therapy is the first-line therapy. However, most cases will eventually develop castration-resistant prostate cancer after androgen deprivation therapy treatment. Enzalutamide is a second-generation androgen receptor antagonist approved by the Food and Drug Administration to treat patients with castrationresistant prostate cancer. Unfortunately, patients receiving enzalutamide treatment will ultimately develop resistance via various complicated mechanisms. This review examines the emerging information on these resistance mechanisms, including androgen receptor-related signalling pathways, glucocorticoid receptor-related pathways and metabolic effects. Notably, lineage plasticity and phenotype switching, gene polymorphisms and the relationship between microRNAs and drug resistance are addressed. Furthermore, potential therapeutic strategies for enzalutamideresistant castration-resistant prostate cancer treatment are suggested, which can help discover more effective and specific regimens to overcome enzalutamide resistance.

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“…Thus, miR-644a can function as an auxiliary agent in the treatment of enzalutamide resistance (Ebron et al, 2019).…”

Section: Cytokine Dysregulationmentioning

confidence: 99%

“…In particular, experiments showed that miR‐644a could sensitize tumours to enzalutamide therapy. Thus, miR‐644a can function as an auxiliary agent in the treatment of enzalutamide resistance (Ebron et al, 2019).…”

Section: Mechanisms Of Enzaluide Resistance In Castration‐resistant Pmentioning

confidence: 99%

Mechanisms of enzalutamide resistance in castration‐resistant prostate cancer and therapeutic strategies to overcome it

Wang

Chen

et al. 2020

British J Pharmacology

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“…The Warburg effect represents the transformation of glucose utilization by tumor cells from oxidative phosphorylation to glycolysis, which is now acknowledged as a major feature of tumors 6,7 . This change in energy metabolism is determined by complex factors, including pressure on the tumor microenvironment and genetic changes [8][9][10][11] . The enhanced glycolysis of tumor cells is mainly due to the increased expression or activity of key glycolysis enzymes 12 .…”

Section: Introductionmentioning

confidence: 99%

A Nomogram Based on Glycolysis-related Gene Expression Profilings Serve as a Novel Prognosis Risk Classifiers for Human Hepatocellular Carcinoma

Zhang

Dai

et al. 2021

Preprint

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Metabolic pattern reconstruction is an important element in tumor progression. The metabolism of tumor cells is characterized by the abnormal increase of anaerobic glycolysis, regardless of the higher oxygen concentration, resulting in a large accumulation of energy from glucose sources, and contributes to rapid cell proliferation and tumor growth which is further referenced as the Warburg effect. We tried to reconstruct the metabolic pattern in the progression of cancer to screen which genetic changes are specific in cancer cells. A total of 12 common types of solid tumors were enrolled in the prospective study. Gene set enrichment analysis (GSEA) was implemented to analyze 9 glycolysis-related gene sets, which are closely related to the glycolysis process. Univariate and multivariate analyses were used to identify independent prognostic variables for the construction of a nomogram based on clinicopathological characteristics and a glycolysis-related gene prognostic index (GRGPI). The prognostic model based on glycolysis genes has the highest area under the curve (AUC) in LIHC (Liver hepatocellular carcinoma). 8-gene signatures (AURKA, CDK1, CENPA, DEPDC1, HMMR, KIF20A, PFKFB4, STMN1) were related to overall survival (OS) and recurrence-free survival (RFS). Further analysis demonstrates that the prediction model can accurately distinguish between high- and low-risk cancer patients among patients in different clusters in LIHC. A nomogram with a well-fitted calibration curve based on gene expression profiles and clinical characteristics improves discrimination in internal and external cohorts. Furthermore, the altering expression of metabolic genes related to glycolysis may contribute to the reconstruction of the tumor-related microenvironment.

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“…19,20 For example, miR-644a was proved to regulate the progression of gastric cancer, hepatocellular carcinoma and breast cancer. 21,22 Studies have found some microRNAs closely related to bladder cancer. 23,24 However, the role of miR-644a in the regulation of bladder cancer remain unknown and it is not clear what specific mechanisms that these microRNAs promote or inhibit the occurrence of bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>Long Non-Coding RNA BCAR4 Binds to miR-644a and Targets TLX1 to Promote the Progression of Bladder Cancer</p>

Wang

et al. 2020

OTT

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Background: Bladder cancer is a serious threat to human health. It is meaningful to study the pathogenesis of bladder cancer. Long non-coding RNAs (lncRNAs) are reported to promote or inhibit bladder cancer development. However, the role of lncRNA BCAR4 in the regulation of bladder cancer remains unclear. Purpose: This study was to explore the role of lncRNA BCAR4 in the progression of bladder cancer cell. Methods: RT-PCR was used to examine the expression of BCAR4 and miR-644a. CCK8 assay, colony formation assay, Transwell assay were used to detect the progression of bladder cancer cells after transfecting of indicated plasmids. Results: The expression of BCAR4 was higher in bladder cancer cell lines than normal urothelial cell line. Moreover, the expression of BCAR4 was associated with the advanced stage and metastasis of bladder cancer. Through knockdown of BCAR4, we discovered that knockdown of BCAR4 significantly decreased the proliferation, migration and invasive abilities of bladder cancer cells. Mechanically, we showed that BCAR4 can bind to miR-644a directly and targets TLX1. Moreover, we also showed that miR-644a was also highly expressed in bladder cancer cells and inhibition of miR-644a or overexpression of TLX1 can increased the migration abilities of bladder cancer caused by knockdown of BCAR4. Conclusion: We showed that BCAR4 sponged miR-644a to modulate the expression of TLX1 and promote bladder cancer development.

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MiR-644a Disrupts Oncogenic Transformation and Warburg Effect by Direct Modulation of Multiple Genes of Tumor-Promoting Pathways

Cited by 41 publications

References 49 publications

Mechanisms of enzalutamide resistance in castration‐resistant prostate cancer and therapeutic strategies to overcome it

Mechanisms of enzalutamide resistance in castration‐resistant prostate cancer and therapeutic strategies to overcome it

A Nomogram Based on Glycolysis-related Gene Expression Profilings Serve as a Novel Prognosis Risk Classifiers for Human Hepatocellular Carcinoma

<p>Long Non-Coding RNA BCAR4 Binds to miR-644a and Targets TLX1 to Promote the Progression of Bladder Cancer</p>

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