&lt;p&gt;miR-4999-5p Predicts Colorectal Cancer Survival Outcome and Reprograms Glucose Metabolism by Targeting PRKAA2&lt;/p&gt;

Zhang, Qiwei; Huang, Zhi; Zhu, Jieyao; Zeng, Chao; Tang, Zhen; Wang, Weiqiang; Huang, He

doi:10.2147/ott.s234666

Cited by 19 publications

(16 citation statements)

References 38 publications

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“…MiR-4999-5p can regulate the glycolysis of the colorectal cancer cells and promote the clone formation, proliferation and invasion of the colorectal cancer cells. The overall survival of the colorectal cancer patients with MiR-4999-5p upregulation is generally low, and MiR-4999-5p upregulation can be used as an independent predictor [12]. However, currently no single glycolysis-related gene signature has been developed to predict the survival of BLCA patients.…”

Section: Discussionmentioning

confidence: 99%

Identifying novel cell glycolysis related gene signature predictive of overall survival in bladder urothelial carcinoma

Zhao¹,

Li²,

Li³

et al. 2020

Preprint

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Background: Bladder urothelial carcinoma (BLCA) is the most common pathological type of bladder cancer and featured by a high risk for relapse and metastasis. Although many biomarkers have been developed by data mining and experimental studies to predict the prognosis of BLCA, a single-gene biomarker usually has poor specificity and sensitivity, leading to unsatisfactory prediction. Therefore, novel gene signatures are needed to more accurately predict the prognosis of BLCA.Methods: Data mining was performed for expression profile analysis of 433 mRNA expression data from the TCGA BLCA patients (n=412). Gene Set Enrichment Analysis (GSEA) was used to interpret the glycolysis-related gene sets. Gene signature related to the prognosis of BLCA was identified by univariate and multivariate Cox regression. A risk score was computed based on three genes by linear regression model and its relation with overall survival was investigated by Kaplan-Meier analysis.Results: Three genes (CHPF, AK3, NUP188) were found to be significantly correlated to the overall survival of BLCA patients. Based on the signature composed of these three genes, 412 BLCA patients were divided into high-risk and low-risk groups. The survival time of the high-risk group was significantly shorter than that of the low-risk group, indicating a worse prognosis.Conclusion: A signature composed of three glycolysis-related genes was developed as biomarkers to predict the prognosis of BLCA and to provide a meaningful reference for the clinical treatment of BLCA.

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Section: Discussionmentioning

confidence: 99%

Identifying novel cell glycolysis related gene signature predictive of overall survival in bladder urothelial carcinoma

Zhao¹,

Li²,

Li³

et al. 2020

Preprint

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“…PRKAA2 , which is the gene that encodes AMPKα2, has been shown to modulate cell proliferation and signalling pathways in different cancers, including bladder [ 87 ], pancreas [ 88 ] and CRC [ 89 ]. Recently, miR-4999-5p has been reported to target PRKAA2 to facilitate metabolic reprogramming in CRC cells [ 38 ]. MiR-4999-5p was highly expressed in CRC tissue samples and associated with poor survival outcome of CRC patients [ 38 ].…”

Section: Role Of Mirnas In Glycolysismentioning

confidence: 99%

“…Recently, miR-4999-5p has been reported to target PRKAA2 to facilitate metabolic reprogramming in CRC cells [ 38 ]. MiR-4999-5p was highly expressed in CRC tissue samples and associated with poor survival outcome of CRC patients [ 38 ]. Overexpression of miR-4999-5p increased cell proliferation rate, glucose uptake, cellular G6P levels, and lactate production in CRC cells [ 38 ].…”

Section: Role Of Mirnas In Glycolysismentioning

confidence: 99%

“…MiR-4999-5p was highly expressed in CRC tissue samples and associated with poor survival outcome of CRC patients [ 38 ]. Overexpression of miR-4999-5p increased cell proliferation rate, glucose uptake, cellular G6P levels, and lactate production in CRC cells [ 38 ]. Correlation analysis and dual-luciferase reporter assays confirmed that miR-4999-5p was negatively correlated with PRKAA2 in a direct manner [ 38 ].…”

Section: Role Of Mirnas In Glycolysismentioning

confidence: 99%

“…Overexpression of miR-4999-5p increased cell proliferation rate, glucose uptake, cellular G6P levels, and lactate production in CRC cells [ 38 ]. Correlation analysis and dual-luciferase reporter assays confirmed that miR-4999-5p was negatively correlated with PRKAA2 in a direct manner [ 38 ]. Glycolysis rate and capacity were restored by PRKAA2 knockdown in miR-4999-5p-silenced CRC cells [ 38 ].…”

Section: Role Of Mirnas In Glycolysismentioning

confidence: 99%

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Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Hon

Abidin

Othman

et al. 2020

Cancers

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Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with a high mortality rate globally. The pathophysiology of CRC is mainly initiated by alteration in gene expression, leading to dysregulation in multiple signalling pathways and cellular processes. Metabolic reprogramming is one of the important cancer hallmarks in CRC, which involves the adaptive changes in tumour cell metabolism to sustain the high energy requirements for rapid cell proliferation. There are several mechanisms in the metabolic reprogramming of cancer cells, such as aerobic glycolysis, oxidative phosphorylation, lactate and fatty acids metabolism. MicroRNAs (miRNAs) are a class of non-coding RNAs that are responsible for post-transcriptional regulation of gene expression. Differential expression of miRNAs has been shown to play an important role in different aspects of tumorigenesis, such as proliferation, apoptosis, and drug resistance, as well as metabolic reprogramming. Increasing evidence also reports that miRNAs could function as potential regulators of metabolic reprogramming in CRC cells. This review provides an insight into the role of different miRNAs in regulating the metabolism of CRC cells as well as to discuss the potential role of miRNAs as biomarkers or therapeutic targets in CRC tumour metabolism.

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Circular CPM promotes chemoresistance of gastric cancer via activating PRKAA2‐mediated autophagy

Fang

Xuan

et al. 2022

Clinical & Translational Med

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Background Chemotherapy can significantly improve the disease‐free survival and overall survival of patients with advanced gastric cancer (GC). 5‐fluorouracil (5‐FU) is frequently applied in the clinic, acting as a first‐line chemotherapy drug of advanced GC, which could be used alone or combining platinum drugs. However, its efficacy is significantly attenuated by chemoresistance, which is associated with patients’ poor survival. Recently, there is evidence suggesting that dysregulation of autophagy may contribute to drug resistance in cancer, and circular RNAs (circRNAs) also take part in chemoresistance. However, whether circRNAs participate in 5‐FU chemoresistance through autophagy remains largely unknown. Methods RNA sequencing technologies and bioinformatics analysis were performed in GC. Sanger sequencing, Actinomycin D assay and RNase R assay confirmed the circular structure of circular CPM (circCPM). Various cell line models and animal models were used to explore related functions in vitro and in vivo. Quantitative Real‐time PCR (qRT‐PCR), fluorescence in situ hybridization, ribonucleic acid; (RNA) pulldown assays, RNA binding protein immunoprecipitation assays and Luciferase reporter assays were applied to explore involved pathways. Results circCPM was up‐regulated in 5‐FU resistant GC cell lines and tissue. Moreover, high circCPM expression is positively associated with poor survival. Silencing circCPM greatly improved chemosensitivity in vitro and in vivo. Mechanistically, it directly binds to miR‐21‐3p in the cytoplasm and therefore increases the expression of PRKAA2, contributing to the activation of autophagy and chemoresistance. Conclusion Our results reveal that circCPM has a crucial role in regulating GC autophagy and 5‐FU resistance by targeting PRKAA2. It may function as a new theory basis for assessing the curative effect of GC and reversing 5‐FU chemoresistance.

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<p>miR-4999-5p Predicts Colorectal Cancer Survival Outcome and Reprograms Glucose Metabolism by Targeting PRKAA2</p>

Cited by 19 publications

References 38 publications

Identifying novel cell glycolysis related gene signature predictive of overall survival in bladder urothelial carcinoma

Identifying novel cell glycolysis related gene signature predictive of overall survival in bladder urothelial carcinoma

Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Circular CPM promotes chemoresistance of gastric cancer via activating PRKAA2‐mediated autophagy

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