STAT5a-targeting miRNA enhances chemosensitivity to cisplatin and 5-fluorouracil in human colorectal cancer cells

Hong, Xuan; Chen, Gongyan; Wang, Meng; Lou, Changjie; Mao, Yinling; Li, Zhiwei; Zhang, Yanqiao

doi:10.3892/mmr.2012.801

Cited by 13 publications

(6 citation statements)

References 25 publications

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“…Furthermore, the overexpression of miR-124 or miR-506 markedly inhibited the ability of SW620 cells to migrate (Figure 2B ), and the overexpression of either miR-124 or miR-506 remarkably attenuated cell invasion in SW620 cells (Figure 2C , five fields were counted in the Matrigel-coated cell invasion experiments). Cisplatin (CDDP) and 5-fluorouracil (5-FU) are usually used to treat CRC [ 39 ]; thus, we measured cell viability to assess the response to these agents. Specifically, we measured the IC50 values using MTT assays.…”

Section: Resultsmentioning

confidence: 99%

miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1

Chen

Liu

et al. 2015

Oncotarget

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miR-124 and miR-506 are reportedly down-regulated and associated with tumor progression in many cancers, but little is known about their intrinsic regulatory mechanisms in colorectal cancer (CRC). In this study, we found that the miR-124 and miR-506 levels were significantly lower in human CRC tissues than in controls, as indicated by qRT-PCR and in situ hybridization histochemistry. We also found that the overexpression of miR-124 or miR-506 inhibited tumor cell progression and increased sensitivity to chemotherapy in vitro. Increased miR-124 or miR-506 expression also inhibited tumor cell proliferation and invasion in vivo. Luciferase reporter assays and western blotting were used to determine the association between miR-124, miR-506 and their target genes, DNMTs. We further identified that miR-124 and miR-506 directly targeted DNMT3B and indirectly targeted DNMT1. The overexpression of miR-124 and miR-506 reduced global DNA methylation and restored the expression of E-cadherin, MGMT and P16. In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC. These findings may provide novel avenues for the development of targeted therapies.

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Section: Resultsmentioning

confidence: 99%

miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1

Chen

Liu

et al. 2015

Oncotarget

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“…Accordingly, fluorescence-activated cell sorting (FACS) analysis was used to assess whether miR-133b contributed to apoptosis in CRC cells. Apoptosis was measured after transfecting miR-133b and siCXCR4 into SW-480 and SW-620 cells for 48 hours, and this was followed by a 24-hour exposure to cisplatin at an appropriate concentration, as previously described [36] (The IC 50 results are not shown). The results revealed a significant increase in apoptosis of SW-620 cells transfected with miR-133b mimics compared to the control transfected cells (the percentage of apoptotic cells increased from 21.31% to 88.37%; Figure 4B; p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression

et al. 2013

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BackgroundMicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion.MethodsMature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines.ResultsA significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells.ConclusionsOur study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC.

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“…Its corresponding protein participates in the signal transduction process by mediating cellular response to ERBB4 [ 31 ]. STAT5A ’s involvement in many cancers, including prostate cancer [ 32 ], oral squamous cell carcinoma [ 33 , 34 ], breast cancer [ 34 ], and colorectal cancer [ 35 ], has been reported. Gab2 (gene: GAB2 ) is an adaptor protein that is important for cancer-signaling transduction processes, including ERK signaling and PI3K-AKT signaling [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening

et al. 2017

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BackgroundIn 2016, it is estimated that there will be 62,700 new cases of kidney cancer in the United States, and 14,240 patients will die from the disease. Because the incidence of kidney renal clear cell carcinoma (KIRC), the most common type of kidney cancer, is expected to continue to increase in the US, there is an urgent need to find effective diagnostic biomarkers for KIRC that could help earlier detection of and customized treatment strategies for the disease. Accordingly, in this study we systematically investigated KIRC’s prognostic biomarkers for survival using the reverse phase protein array (RPPA) data and the high throughput sequencing data from The Cancer Genome Atlas (TCGA).ResultsWith comprehensive data available in TCGA, we systematically screened protein expression based survival biomarkers in 10 major cancer types, among which KIRC presented many protein prognostic biomarkers of survival time. This is in agreement with a previous report that expression level changes (mRNAs, microRNA and protein) may have a better performance for prognosis of KIRC. In this study, we also identified 52 prognostic genes for KIRC, many of which are involved in cell-cycle and cancer signaling, as well as 15 tumor-stage-specific prognostic biomarkers. Notably, we found fewer prognostic biomarkers for early-stage than for late-stage KIRC. Four biomarkers (the RPPA protein IDs: FASN, ACC1, Cyclin_B1 and Rad51) were found to be prognostic for survival based on both protein and mRNA expression data.ConclusionsThrough pan-cancer screening, we found that many protein biomarkers were prognostic for patients’ survival in KIRC. Stage-specific survival biomarkers in KIRC were also identified. Our study indicated that these protein biomarkers might have potential clinical value in terms of predicting survival in KIRC patients and developing individualized treatment strategies. Importantly, we found many biomarkers in KIRC at both the mRNA expression level and the protein expression level. These biomarkers shared a significant overlap, indicating that they were technically replicable.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-4026-6) contains supplementary material, which is available to authorized users.

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STAT5a-targeting miRNA enhances chemosensitivity to cisplatin and 5-fluorouracil in human colorectal cancer cells

Cited by 13 publications

References 25 publications

miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1

miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1

miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression

Unique protein expression signatures of survival time in kidney renal clear cell carcinoma through a pan-cancer screening

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