miR-27a-3p targeting RXRα promotes colorectal cancer progression by activating Wnt/β-catenin pathway

Liang, Jiangtao; Tang, Jianming; Shi, Huijuan; Li, Hui; Zhen, Tiantian; Duan, Jing; Kang, Lili; Zhang, Fenfen; Dong, Yu; Han, Anjia

doi:10.18632/oncotarget.19635

Cited by 57 publications

(35 citation statements)

References 29 publications

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“…Finally, miR-27a positively influences the Wnt/β−catenin pathway that is pivotal in colorectal tumorigenesis, via PPARγ, RXRα and SRFP1. [47][48][49] We have shown and confirmed here that PPARγ is a miR-27a direct target along with RXRα and SFRP1, two previously validated ones, all implicated in the control of this pathway ( Supplementary Fig. 2B).…”

Section: P-ampk/ampk Ratio Increased While the P-mtor/mtor Ratio Sligsupporting

confidence: 83%

“…Importantly, the data presented suggest that miR-27a establishes cross-talks with activated oncogenes such as AKT and K-RAS/ B-RAF 37,40,41 via PTEN and Sprouty2, two direct targets of miR-27a, 40,42 contributing to modulate these pathways, notwithstanding the presence of mutations of the driving oncogenes. Likewise, they indicate that miR-27a establishes a regulatory axis with cMYC through FBXW7 44 and with the Wnt/β-catenin pathway through PPARγ, RXRα and SFRP1, [47][48][49] all direct targets. Thus, miR-27a coordinates and modulates oncogenes-driven and tumourassociated pathways to reprogramme cell homoeostasis towards a more proliferating and aggressive phenotype.…”

Section: Discussionmentioning

confidence: 99%

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miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

et al. 2020

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BACKGROUND: Metabolic reprogramming towards aerobic glycolysis in cancer supports unrestricted cell proliferation, survival and chemoresistance. The molecular bases of these processes are still undefined. Recent reports suggest crucial roles for microRNAs. Here, we provide new evidence of the implication of miR-27a in modulating colorectal cancer (CRC) metabolism and chemoresistance. METHODS: A survey of miR-27a expression profile in TCGA-COAD dataset revealed that miR-27a-overexpressing CRCs are enriched in gene signatures of mitochondrial dysfunction, deregulated oxidative phosphorylation, mTOR activation and reduced chemosensitivity. The same pathways were analysed in cell lines in which we modified miR-27a levels. The response to chemotherapy was investigated in an independent cohort and cell lines. RESULTS: miR-27a upregulation in vitro associated with impaired oxidative phosphorylation, overall mitochondrial activities and slight influence on glycolysis. miR-27a hampered AMPK, enhanced mTOR signalling and acted in concert with oncogenes and tumour cell metabolic regulators to force an aerobic glycolytic metabolism supporting biomass production, unrestricted growth and chemoresistance. This latter association was confirmed in our cohort of patients and cell lines. CONCLUSIONS: We disclose an unprecedented role for miR-27a as a master regulator of cancer metabolism reprogramming that impinges on CRC response to chemotherapy, underscoring its theragnostic properties.

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Section: P-ampk/ampk Ratio Increased While the P-mtor/mtor Ratio Sligsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

et al. 2020

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“…Here, we found that exosomal miR-27a and miR-130a in plasma were novel potential prognostic biomarkers of colorectal cancer, and positively associated with TNM stage and histologic grade. RXRa, SMAD2, SMAD4, and SFRP1 were reported as targets of miR-27a, and these targets are related with known Wnt/b-catenin and TGFb pathways (32)(33)(34). Nkd2, which is significantly associated with Wnt/b-catenin pathway, was demonstrated to be a target of miR-130a (35).…”

Section: Discussionmentioning

confidence: 96%

“…31). Liang and colleagues identified that miR-27a targets RXRa to promote colorectal cancer cells progression by activating Wnt/b-catenin pathway (32). Although, miR-27a and miR-130a have been reported to be onco-miRNAs in colorectal cancer, whether circulating exosomal miR-27a and miR-130a could be used to predict the prognosis of colorectal cancer patients are still elusive.…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

Liu

Pan

Sun

et al. 2018

Cancer Epidemiology, Biomarkers &Amp; Prevention

108

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Colorectal cancer is one of the most common cancers worldwide usually is associated with poor prognosis due to the advanced stage when diagnosed. This study aimed to investigate whether specific circulating exosomal miRNAs could act as biomarkers for early diagnosis of colorectal cancer. A total of 369 peripheral blood samples were included in this study. In the discovery phase, circulating exosomal miR-27a and miR-130a were selected after synthetical analysis of two GEO datasets and TCGA database. The differential expression and diagnostic utility of miR-27a and miR-130a panel were validated using qRT-PCR and ROC curve analysis in subsequent training phase, validation phase, and external validation phase. The prognosis of circulating exosomal miR-27a and miR-130a were investigated using the Kaplan-Meier method. The expression of exosomal miR-27a and miR-130a in plasma significantly increased in colorectal cancer. The area under ROC curves (AUC) of miR-27a (miR-130a) were 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase, and 0.746 (0.697) in the external validation phase. The combination of two miRNAs presented higher diagnostic utility for colorectal cancer (AUCs = 0.846, 0.898, and 0.801 for the training, validation, and external validation phases, respectively). Patients with colorectal cancer with high expression of circulating exosomal miR-27a or miR-130a underwent poorer prognosis. We identified a circulating exosomal miRNAs panel for the detection of colorectal cancer. The exosomal miR-27a and miR-130a panel in plasma may act as a noninvasive biomarker for early detection and predicting prognosis of colorectal cancer. .

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“…MiR-27a: miR-27a promotes CRC proliferation, migration, and invasion by downregulation of RXRα [138]. RXRα interacts with β-catenin and suppresses the Wnt/β-catenin signaling pathway [139].…”

Section: Pro-angiogenic Mirnas In Crcmentioning

confidence: 99%

Angioregulatory microRNAs in Colorectal Cancer

Soheilifar

Grusch

Neghab

et al. 2019

Cancers

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Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.

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miR-27a-3p targeting RXRα promotes colorectal cancer progression by activating Wnt/β-catenin pathway

Cited by 57 publications

References 29 publications

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer

Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

Angioregulatory microRNAs in Colorectal Cancer

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