The deoxycholic acid targets miRNA-dependent CAC1 gene expression in multidrug resistance of human colorectal cancer

Kong, Ying; Bai, Pei-song; Sun, Huizhen; Kang, Nan; Chen, Nanzheng; Qi, Xu

doi:10.1016/j.biocel.2012.08.006

Cited by 35 publications

(28 citation statements)

References 19 publications

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“…Taken together, the published studies suggest that downregulated CCNA2 and CACUL1 may be involved in cell apoptosis. Some studies have reported that CCNA2 and CACUL1 are regulated by other miRNAs (Kong et al ; Yang et al ). However, the biological function of CCNA2 and CACUL1 in TBI, in particular, the function regulated by miR‐219a‐5p, has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Yan

et al. 2019

Journal of Neurochemistry

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Circulating microRNAs (miRNAs) have emerged as diagnostic and prognostic biomarkers for traumatic brain injury (TBI). However, a comprehensive characterization of the serum miRNA profile in patients with TBI and the roles of these potential markers in neuronal regulation have rarely been reported. In this study, the levels of 754 serum miRNAs were initially determined in two pooled samples of 15 severe traumatic brain injury (sTBI) patients and 15 healthy controls using a TaqMan Low Density Array. The markedly upregulated miRNAs in sTBI patients were subsequently validated individually by quantitative reverse-transcription PCR (RT-qPCR) in another larger cohort consisting of 81 sTBI patients, 81 mild traumatic brain injury (mTBI) patients and 82 age/sex-matched healthy controls. Seven miRNAs, including miR-103a-3p, miR-219a-5p, miR-302d-3p, miR-422a, miR-518f-3p, miR-520d-3p and miR-627, were significantly upregulated in both sTBI and mTBI patients compared with their expression in controls. Among these miRNAs, miR-219a-5p not only discriminated sTBI and mTBI patients from controls but also discriminated between sTBI and mTBI patients. We further show here that in the neuronal cell injury model, upregulated miR-219a-5p inhibits the expression of CCNA2 and CACUL1 and further regulates akt/Foxo3a and p53/Bcl-2 signaling pathways, causing a notable change in the expression of cleaved caspase-3, thereby inducing neuronal apoptosis. These results indicate that these seven selected miRNAs could serve as novel biomarkers for TBI. In particular, miR-219a-5p is a potentially valuable indicator of the diagnosis, prognosis of TBI and appears to regulate neuronal apoptosis and death. Keywords: biomarker, CACUL1, CCNA2, microRNA, miR-219a-5p, traumatic brain injury.

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Section: Discussionmentioning

confidence: 99%

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Yan

et al. 2019

Journal of Neurochemistry

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“…The increased intestinal level of DCA after a high-fat diet is associated with the onset of many intestinal diseases including colorec-tal cancer. [30][31][32] However, the mechanism still remains to be elucidated. In the present study, we investigated the effects of DCA on the intestinal mucosal barrier and its role in the development of CRC.…”

Section: Discussionmentioning

confidence: 99%

Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis

et al. 2018

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“…Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation, resulting sensitization of cancer cells to chemotherapy [41]. Also, miR-199a-5p is related to multidrug resistance in colon cancer [42] and it is upregulated in cisplatin-sensitive ovarian cancer cells [43]. In this study, we have established a robust tumor-suppressive role of miR-199a-5p in TNBC via modulation of EMT genes and stem cancer markers, further investigation effort should be placed on the altered chemotherapy sensitivity and hence might help in selecting a more suitable chemotherapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

miR-199a-5p confers tumor-suppressive role in triple-negative breast cancer

et al. 2016

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BackgroundTriple-negative breast cancer (TNBC) remains a poor prognostic factor for breast cancer since no effective targeted therapy is readily available. Our previous studies confirmed miR-199a-5p is a TNBC-specific circulating biomarker, however, its functional roles in breast cancer is largely unknown. Thus, we investigated the functional implication of miR-199a-5p in TNBC and its potential underlying mechanisms.MethodsMTT assay was performed to investigate the cell proliferation after transient transfection of miR-199a-5p in MDA-MB-231 cell line, followed by cell cycle analysis. Transwell invasion assay and wound healing assay were used to study the invasion and migration ability respectively. To further investigate the stemness-related characteristics of miR-199a-5p in breast cancer cells, single-cell clonogenic assay and aldehyde dehydrogenase (ALDH) assay were performed. 32 normal and 100 breast cancer patients’ plasma were recruited to identify the potential circulating markers by qPCR.ResultsCell proliferation assay revealed significant inhibition after miR-199a-5p ectopic expression (p < 0.0001), as a result of decreased S phase (p = 0.0284), increased G0/G1 phase (p = 0.0260) and apoptosis (p = 0.0374). Invasiveness (p = 0.0005) and wound healing ability were also decreased upon miR-199a-5p overexpression. It significantly altered EMT-related genes expression, namely CDH1, ZEB1 and TWIST. Single-cell clonogenic assay showed decreased colonies in miR-199a-5p (p = 0.0182). Significant downregulation (p = 0.0088) and inhibited activity (p = 0.0390) of ALDH was observed in miR-199a-5p. ALDH1A3, which is the dominant isoform of ALDH, is significantly upregulated in breast cancer plasma especially in TNBC (p = 0.0248). PIK3CD was identified as a potential downstream target of miR-199a-5p.ConclusionsTaken together, we unraveled, for the first time, the tumor-suppressive role of miR-199a-5p in TNBC, which attributed to EMT and cancer stemness properties, providing a novel therapeutic options towards this aggressive disease.

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The deoxycholic acid targets miRNA-dependent CAC1 gene expression in multidrug resistance of human colorectal cancer

Cited by 35 publications

References 19 publications

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis

miR-199a-5p confers tumor-suppressive role in triple-negative breast cancer

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