miR‐210‐3p mediates metabolic adaptation and sustains DNA damage repair of resistant colon cancer cells to treatment with 5‐fluorouracil

Pranzini, Erica; Leo, Angela; Rapizzi, Elena; Ramazzotti, Matteo; Magherini, Francesca; Giovannelli, Lisa; Caselli, Anna; Cirri, Paolo; Taddei, Maria Letizia; Paoli, Paolo

doi:10.1002/mc.23107

Cited by 12 publications

(6 citation statements)

References 39 publications

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“…Similarly, exosome-mediated transfer of miR-210-3p promotes lung cancer cell invasion by activating STAT3 signaling-induced EMT 27 . In colon cancer, miR-210-3p was reported to sustain DNA damage repair by metabolic adaptation 28 . Moreover, miR-210-3p is predictive of clear-cell renal cell carcinoma recurrence, pointing to potential utility as biomarkers 29 .…”

Section: Discussionmentioning

confidence: 99%

A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer

Wei

et al. 2020

Cell Death Dis

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Reprogrammed energy metabolism, especially the Warburg effect (aerobic glycolysis), is an emerging hallmark of cancer. Different from other breast cancer subtypes, triple-negative breast cancer (TNBC) exhibits high metabolic remodeling, increased aggressiveness and lack of targeted therapies. MicroRNAs (miRNA) are essential to TNBC malignant phenotypes. However, little is known about the contribution of miRNA to aerobic glycolysis in TNBC. Through an integrated analysis and functional verification, we reported that several miRNAs significantly correlates to the Warburg effect in TNBC, including miR-210-3p, miR-105-5p, and miR-767-5p. Ectopic expression of miR-210-3p enhanced glucose uptake, lactate production, extracellular acidification rate, colony formation ability, and reduced serum starvation-induced cell apoptosis. Moreover, GPD1L and CYGB were identified as two functional mediators of miR-210-3p in TNBC. Mechanistically, miR-210-3p targeted GPD1L to maintain HIF-1α stabilization and suppressed p53 activity via CYGB. Ultimately, miR-210-3p facilitated aerobic glycolysis through modulating the downstream glycolytic genes of HIF-1α and p53. Taken together, our results decipher miRNAs that regulate aerobic glycolysis and uncover that miR-210-3p specifically contributes to the Warburg effect in TNBC.

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Section: Discussionmentioning

confidence: 99%

A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer

Wei

et al. 2020

Cell Death Dis

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“…MiR-210 is a hypoxia-induced miRNA [77,78] and associated with radio-resistance in lung cancer [79]. Moreover, miR-210-3p was shown to be downregulated in colorectal cancer cells treated with 5-fluorouracil (5-FU), leading to an adaptation of cancer cells during treatment and enhancing chemotherapy resistance [80]. While the role of miR-210 is well studied during hypoxia, cancer progression and therapy, potential miRNA-independent functions of its host gene MIR210HG are less studied.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Signatures of a Preclinical Mouse Model during Colorectal Cancer Progression under Low-Dose Metronomic Chemotherapy

Ho-Xuan

Lehmann

Glažar

et al. 2020

Cancers

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Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy.

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“…Recently, it has been found that the number of miRNAs regulated by HIF-1α mediates changes in cell metabolism [51], and the most studied hypoxia-induced miRNA is miR-210 [52,53]. HIF-1α-induced miR-210 is observed in many cell types, and it has been described as being involved in broad cancer pathologies, including DNA repair [54], survival [55], proliferation [56], metastasis [57], epithelial-mesenchymal transition (EMT) [58], angiogenesis [59], and radioresistance [60]. In oropharyngeal squamous cell carcinomas (OPSCC), iron-sulfur cluster assembly protein (ISCU) has been confirmed as a target of the HIF-1α-induced miR-210 [38].…”

Section: Mir-210mentioning

confidence: 99%

MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

Shiah

Chou

Chang

2021

Cancers

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MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that negatively regulate gene expression by binding to target mRNAs. Deregulated miRNAs can act as either oncogenic miRNAs or tumor suppressor miRNAs in controlling proliferation, differentiation, apoptosis, metastasis, epithelial–mesenchymal transition, and immune responses, which are all involved in the carcinogenesis process of HNSCC. Recent findings have shown that metabolic reprogramming is an important hallmark of cancer, which is necessary for malignant transformation and tumor development. Some reprogrammed metabolisms are believed to be required for HNSCC against an unfavorable tumor microenvironment (TME). The TME is composed of various cell types embedded in the altered extracellular matrix, among which exosomes, secreted by cancer cells, are one of the most important factors. Tumor-derived exosomes reshape the tumor microenvironment and play a crucial role in cell-to-cell communication during HNSCC development. Exosomes encapsulate many biomolecules, including miRNAs, circulate in body fluids, and can transmit intercellular regulatory messages to nearby and distant sites, which indicates that exosomal miRNAs have the potential to become non-invasive biomarkers. This review aims to clarify the functions of diverse miRNAs in HNSCC metabolic reprogramming and tumor-derived exosomes. In addition, it also emphasizes the potential role of miRNA as a biomarker in the diagnosis, prognosis, and treatment of HNSCC cancer.

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miR‐210‐3p mediates metabolic adaptation and sustains DNA damage repair of resistant colon cancer cells to treatment with 5‐fluorouracil

Cited by 12 publications

References 39 publications

A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer

A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer

Gene Expression Signatures of a Preclinical Mouse Model during Colorectal Cancer Progression under Low-Dose Metronomic Chemotherapy

MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

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