The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

Bălăcescu, Ovidiu; Sur, Daniel; Căinap, Călin; Vișan, Simona; Cruceriu, Daniel; Manzat-Saplacan, Roberta M; Muresan, Mihai-Stefan; Bălăcescu, Loredana; Lisencu, Cosmin; Irimie, Alexandru

doi:10.3390/ijms19123711

Cited by 111 publications

(91 citation statements)

References 145 publications

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“…Emerging evidence in the past decades has demonstrated aberrant expression of numerous miRNAs in cRc (16,25,26). Moreover, miRNA dysregulation has been shown to play a significant role in the oncogenicity of CRC by regulating all aspects of aggressive cell behavior, such as proliferation, division, apoptosis, metastasis and angiogenesis (15,27,28). Therefore, in-depth exploration of cancer-associated miRNAs in CRC may provide novel insights into the mechanism underlying CRC development and progression and may facilitate the identification of promising diagnostic and therapeutic targets Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6

Yan

Zhao

et al. 2019

Int J Mol Med

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Aberrant expression of numerous microRNAs (miRNAs/miRs) in colorectal cancer (cRc) significantly affects disease progression. Recently, miR-629-5p (miR-629) was identified as a tumor-promoting miRNA in the malignant processes of a number of human cancers. However, few studies have been conducted regarding expression profiles and detailed roles of miR-629 in CRC. In the present study, reverse transcription-quantitative polymerase chain reaction was used to assess miR-629 expression in cRc tissues and cell lines. cell Counting Kit-8 assay, flow cytometry and Transwell assays were performed to determine the in vitro effects of miR-629 on CRC cell proliferation, apoptosis, and metastasis, respectively. Xenograft models were employed to determine the in vivo effects of miR-629 on tumor growth in nude mice. Molecular mechanisms underlying the activity of miR-629 in CRC cells were explored. miR-629 expression decreased in cRc tissues and cell lines. The decreased aberrant miR-629 expression was significantly associated with tumor size, lymphatic metastasis and tumor-node-metastasis stage of cRc, and was a predictor of poor prognosis. Restoring miR-629 expression attenuated cRc cell proliferation, migration and invasion; promoted cell apoptosis in vitro; and inhibited tumor growth in vivo. Low-density lipoprotein receptor-related protein 6 (LRP6) was a direct target gene of miR-629 in CRC cells. Furthermore, the effect of LRP6 knockdown was similar to that of miR-629 overexpression in CRC cells. Restoration of LRP6 expression neutralized the effects of miR-629 in CRC cells. miR-629 suppressed the activation of the Wnt/β-catenin pathway through LRP6 regulation both in vitro and in vivo. In conclusion, miR-629 suppressed the development and progression of CRC by directly targeting LRP6 and inhibiting the Wnt/β-catenin pathway both in vitro and in vivo. Therefore, miR-629 may be a novel prognostic biomarker and therapeutic target in CRC.

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Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6

Yan

Zhao

et al. 2019

Int J Mol Med

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“…MicroRNAs (miRNAs) are a family of short, single‐stranded, and noncoding RNAs which modulate the expression of target genes and exert important roles within diverse biological courses containing cellular growth, proliferation, development, differentiation, angiogenesis, metabolism, and apoptosis . Growing studies have identified that dysregulation of miRNAs participated in the tumorigenesis and progression of CRC . Meanwhile, miRNAs commonly exist in tissue, blood, urine, and feces, and can be easily detected.…”

Section: Introductionmentioning

confidence: 99%

Identification of microRNA‐181 as a promising biomarker for predicting the poor survival in colorectal cancer

Peng

Yao

et al. 2019

Cancer Medicine

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Background A series of studies have investigated the vital role of microRNA‐181 (miR‐181) in the initiation and development of colorectal cancer (CRC), and demonstrated that it might be associated with the prognosis of CRC. However, inconsistent findings have hindered its clinical application. Methods A comprehensive meta‐analysis and an integrative bioinformatics analysis were carried out for concluding current available evidence, clarifying the preliminary prognostic value and unfolding the underlying biological function of miR‐181 in CRC patients. Results The findings revealed that elevated expression levels of miR‐181 were associated with significantly poorer overall survival rates (HR = 1.75, 95% CI: 1.26‐2.43, P < .05). Meanwhile, the target genes of miR‐181 were identified and enriched into several important gene ontology (GO) categories and signaling pathways including miRNAs in cancer, pathways in cancer, proteoglycans in cancer, colorectal cancer, FoxO signaling pathway, PI3K‐Akt signaling pathway, VEGF signaling pathway, HIF‐1 signaling pathway, mTOR signaling pathway, and cAMP signaling pathway, which were confirmed highly involved in the initiation and progression of CRC. In addition, the protein‐protein interaction (PPI) networks were set up by miR‐181 targets to screen hub nodes and significant modules, which were also considerably associated with the molecular pathogenesis of CRC. Conclusions The present study demonstrated that miR‐181 could be a promising biomarker with predictive value for prognosis for CRC patients. However, future studies comprising large cohorts from multicenter are warranted to further investigate the biomarker value of miR‐181.

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“…Metastasis, the major cause of death in CRC, results from multi-step processes, including angiogenesis, invasion, circulation, extravasation, and metastatic colonization (Tauriello et al, 2017;Qi and Ding, 2018). Accumulating evidence demonstrated that miRNA plays a crucial role in metastasis (Guo et al, 2017;Hur et al, 2017;Balacescu et al, 2018;Ozawa et al, 2018). Therefore, the mechanism of miRNA underlying CRC metastasis might generate a miRNA-based target for diagnosis and therapeutics of CRC (Ji et al, 2018;Li et al, 2018;Zhao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-654-3p in Colorectal Cancer Indicates Poor Prognosis and Promotes Cell Proliferation and Invasion by Targeting SRC

et al. 2020

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Background: MicroRNAs (miRNAs), such as miR-654-3p, regulate gene expression at the post-transcriptional level affecting malignant tumor behavior. However, the expression levels, function, and mechanism of miR-654-3p in colorectal cancer (CRC) are unknown. Methods: The expression levels of miR-654-3p and SRC in 103 CRC tissues and matched normal colorectal tissues were detected by a quantitative real-time polymerase chain reaction (qRT-PCR). miR-654-3p was overexpressed by RNA mimics and SRC knockdown by siRNA. Function-based experiments were carried out to detect the proliferation and migration abilities in CRC cell lines. Flow cytometry assay was performed to evaluate the effect of miR-654-3p on cell apoptosis and cycle distribution. Xenograft tumor models in nude mice were utilized to evaluate miR-654-3p functions in vivo. Dual-fluorescence reporter assay was used to verify the direct binding between miR-654-3p and SRC. Results: miR-654-3p was downregulated in CRC tissues as compared to matched normal colorectal tissues. The expression levels of miR-654-3p were closely associated with distant metastasis. In addition, elevated expression of miR-654-3p in CRC patients prolonged the overall survival. Upregulated miR-654-3p significantly suppressed the proliferation and migration capacity of CRC cells by enhancing apoptosis and promoting G0/G1 phase arrest. The direct binding between miR-654-3p and SRC was verified by the dual-luciferase reporter gene. Furthermore, the suppression of proliferation and migration capacity by elevated miR-654-3p level could be reversed by overexpressing SRC. Conclusion: miR-654-3p acts as a tumor suppressor through regulating SRC. It might also serve as a diagnostic and prognostic indicator and a novel molecular target for CRC therapy.

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The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

Cited by 111 publications

References 145 publications

Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6

Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6

Identification of microRNA‐181 as a promising biomarker for predicting the poor survival in colorectal cancer

Downregulation of miR-654-3p in Colorectal Cancer Indicates Poor Prognosis and Promotes Cell Proliferation and Invasion by Targeting SRC

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