Decreased expression of miR-874 and its tumor suppressive function in human colorectal cancer

Wang, X J; Xia, Microgene; Bi, Wenzhi

doi:10.4238/gmr.15028077

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…Up-regulation of miR-874 weakened the colony-forming ability of CRC cells and increased the sensitivity of CRC cells to 5-fluorouracil. Wang et al 21 suggested miR-874 to be a novel therapeutic target for CRC, and low expression of miR-874 in CRC was an independent predictor of low survival. Results from this article also revealed that, as a tumor suppressor, miR-874 expression was reduced in CRC and was directly inhibited by circ_0005576.…”

Section: Discussionmentioning

confidence: 99%

<p>Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer</p>

Chen¹,

Li²,

Hu³

2020

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Purpose: To investigate the function of circ_0005576 in colorectal cancer (CRC) progression. Patients and Methods: Circ_0005576 expression in CRC patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). CRC cells were transfected using Lipofectamine 2000 reagent. CRC cell proliferation was researched by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2-deoxy-uridine (EdU) incorporation experiment. Cell cycle and apoptosis were determined by flow cytometry analysis. Luciferase reporter assay was used to explore the relationship between circ_0005576 and miR-874 or between miR-874 and CDK8. qRT-PCR and Western blot were used to detect circ_0005576, miR-874, and CDK8 expression. In vivo experiments were performed using nude mice. CDK8 and Ki67 expression in xenograft tumors was investigated by immunohistochemistry. Tunel assay was conducted to analyze the apoptosis of xenograft tumors. Results: Circ_0005576 expression was up-regulated in CRC, which was associated with tumor progression (P < 0.05 or P < 0.01). Circ_0005576 knockdown in CRC cells reduced proliferation, induced apoptosis, increased cells in the G1 phase, and decreased cells in the S phase (P < 0.01 or P < 0.001). Circ_0005576 promoted CDK8 expression via sponging miR-874. miR-874 knockdown and CDK8 overexpression significantly reversed the inhibitory effect of circ_0005576 knockdown on CRC cells malignant phenotype (P < 0.05 or P < 0.01). Circ_0005576 knockdown inhibited tumor growth in vivo (P < 0.01). Circ_0005576 knockdown reduced CDK8, Ki67 expression, and enhanced apoptosis in xenograft tumors. Conclusion: Circ_0005576 promoted malignant progression through the miR-874/CDK8 axis in CRC.

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Section: Discussionmentioning

confidence: 99%

<p>Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer</p>

Chen¹,

Li²,

Hu³

2020

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Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway

et al. 2017

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Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR-874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect. Furthermore, our results demonstrated that miR-874-3p directly inhibited the expression of transcriptional co-activators YAP and TAZ of the Hippo signaling pathway, resulting in the inactivation of the TEAD transcription. Thus, our findings clarify a novel mechanism by which miR-874-3p restores chemotherapeutic sensitivity of CRC to 5-FU, indicating that offering miR-874-3p mimics in combination with 5-FU may serve as a new therapeutic strategy to circumvent the chemoresistance in CRC.

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Decreased expression of miR-874 and its tumor suppressive function in human colorectal cancer

Cited by 2 publications

References 23 publications

<p>Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer</p>

<p>Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer</p>

Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway

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