MicroRNAs in colorectal cancer: Small molecules with big functions

Yao, Xuan; Yang, Huiliang; Zhao, Linjie; Lau, Wayne Bond; Lau, Bonnie; Ren, Ning; Hu, Yanfei; Yi, Tao; Zhao, Xia; Zhou, Shengtao; Wei, Yuquan

doi:10.1016/j.canlet.2014.11.051

Cited by 79 publications

(53 citation statements)

References 184 publications

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“…miRNAs are essential for the regulation of many biological processes, such as the cell cycle, proliferation, differentiation and apoptosis [6–8]. Moreover, accumulating evidence has implicated miRNAs in various pathological conditions, including cancer [9, 10]. Deregulated miRNAs have been found to be associated with tumor initiation, promotion and progression by acting on many oncogenes and tumor suppressors.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

Wen

Liu

et al. 2016

Oncotarget

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microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR-375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/β-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

Wen

Liu

et al. 2016

Oncotarget

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“…miRNAs are capable of modulating cell proliferation, differentiation, metabolism, apoptosis, and thus actively participate in regulating tumorigenesis and tumor progression. 8, 9 Evidence suggests that miRNA can modulate the therapeutic efficacy in several cancer types, 10 but it is still unclear whether and how deregulated miRNAs are involved in the chemoresistance of GBC. miR-218-5p, a tumor suppressor miRNA, has been found to be downregulated in several cancer types such as GBC, cervical cancer, colon cancer, and prostate cancer.…”

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confidence: 99%

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer

Wang

Zhan

et al. 2017

Cell Death Dis

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Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were significantly lower in GBC than adjacent non-cancer tissues, and which were also associated with patient prognosis. While miR-218-5p overexpression abrogated gemcitabine resistance of GBC cells, silencing of which exhibited the opposite effects. Via six microRNA targets prediction algorithms, we found that PRKCE is a potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the luciferase activity of reporter constructs containing 3′-UTR of PRKCE and also reduced PRKCE expression. Further studies revealed that miR-218-5p promotes sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of MDR1/P-gp. Taken together, our results imply that an intimate correlation between miR-218-5p and PRKCE/MDR1 axis abnormal expression is a key determinant of gemcitabine tolerance, and suggest a novel miR-218-5p-based clinical intervention target for GBC patients.

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“…Indeed, deregulations of a few miRNAs have been proved in the CRC tumorigenesis in previous studies. Of those most widely investigated miRNAs, some are classified as oncogenes in CRC, such as miR-21, miR-155, miR-31 and miR-92a, while others are considered as tumor suppressors represented by Let-7, miR-143, miR-145 and miR-215 [7,8].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

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Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

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MicroRNAs in colorectal cancer: Small molecules with big functions

Cited by 79 publications

References 184 publications

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

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