Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets

Ji, Lin; Chuang, Chia Chen; Zuo, Li

doi:10.18632/oncotarget.14461

Cited by 55 publications

(40 citation statements)

References 210 publications

(142 reference statements)

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“…The development of colorectal cancer is a complex and multi-stage process, characterized by various interactions between environmental carcinogens, genetic modifications and the host immune system (15). Dense infiltration of cytokine-producing immune/inflammatory cells frequently result in the aberrant activation of multiple intracellular signal transduction cascades, ultimately resulting in the uncontrolled growth of transformed cells.…”

Section: Introductionmentioning

confidence: 99%

Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways

et al. 2017

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Abstract. The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks. At present, anti-tumor agents are often single-targeted and therefore are not always therapeutically effective. Moreover, long-term use of these anti-tumor agents often generates drug resistance and potential side effects. These problems highlight the urgent need for the development of novel and more effective anti-cancer drugs. Hedyotis diffusa Willd (HDW) has been used as a major component in traditional Chinese medicine for the clinical treatment of colorectal cancer, with a limited number of adverse effects. However, the molecular mechanisms, which underlie its anti-cancer activity, still require further elucidation. In the present study, using xenograft models and various different human CRC cell lines, the efficacy of the ethanol extract of HDW (EEHDW) against tumor growth was evaluated, and its underlying molecular mechanisms of action were investigated. It was demonstrated that EEHDW was able to inhibit cancer growth in vivo and in vitro. Furthermore, EEHDW was able to suppress the activation of several CRC-associated signaling pathways and was able to regulate the expression of various inflammatory and angiogenic factors. This resulted in the induction of apoptosis and inhibition of cellular proliferation, as well as tumor angiogenesis. The present study demonstrated that EEHDW is able to exhibit anti-cancer activity due to its ability to affect multiple intracellular targets, which suggests that it may be a novel multi-potent therapeutic agent for the treatment of colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways

et al. 2017

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“…Also, treatment of EOC cells with H 2 O 2 caused a dose and time-dependent decrease in miR-29b levels of EOC cells, suggesting miR-29b close involvement in EOC oxidative metabolism. Accumulating studies have revealed that ROS can alter the expression of certain miRNAs [33, 34]. The mechanism underlying ROS-regulated microRNA expression is complicated and poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Hou

Zuo

et al. 2017

Cell Physiol Biochem

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Background: Metabolic abnormalities are frequently observed in multiple malignancies including epithelial ovarian cancer (EOC), among which imbalance between generation and elimination of reactive oxygen species (ROS) plays a critical role in EOC onset and progression. Here we investigated the role of miR-29b, a well-established tumor-suppressor miRNA in metabolic regulation of EOC cells. Methods: cell viability and apoptosis in miR-29b inhibited and over-expressed EOC cells were evaluated by CCK8 and Annexin V–FITC/PI assays. Change in miR-29b was detected in EOC cells incubated in H₂O₂ culture by q-PCR. Relative ROS levels were also detected in different EOC cultures, including modified miR-29b and SIRT1 levels as well as H₂O₂ incubation. A luciferase reporter assay was employed to detect the direct binding of miR-29b to SIRT1 3’ UTR. Changes in cell viability and ROS levels were assessed in SIRT1-knocked down EOC cells. Results: miR-29b expression correlates with decreased EOC cell viability and increased apoptosis. H₂O₂ downregulated miR-29b in a time and dose-dependent manner. miR-29b expression negatively correlated with ROS levels, whereas SIRT1 significantly stimulated ROS formation. Luciferase reporter assays confirmed miR-29b downregulation of SIRT1by directly targeting its mRNA 3’-UTR. SIRT1 silencing rescues cell viability of H₂O₂ treated cells. Also, SIRT1 inhibition blocked cell apoptosis induced by H₂O₂ as well as reduced intracellular ROS levels. Conclusion: Together, our findings indicated that the miR-29b/SIRT1 axis has a protective effect against H₂O₂-induced damage of cell viability and oxidative stress and may provide novel options for miR-29b-based therapeutic approaches for EOC treatment.

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“…Both Lin et al9 and Yantiss et al10 found that the miR-203 level in cancerous tissues was significantly higher than that in adjacent normal tissues, and the prognosis was poor if high levels of miR-203 were present. In contrast, Chiang et al11 reported opposite results in 212 clinical specimens of colorectal cancers; they found that the miR-203 level in cancer tissue was lower than in the adjacent areas and 5-year survival rate of patients with lower miR-203 was worse.…”

Section: Introductionmentioning

confidence: 99%

miR-203 as a novel biomarker for the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis

Hao

Wang

et al. 2017

OTT

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We sought to systematically evaluate the diagnostic and prognostic value of miR-203 in patients with colorectal cancer. To explore the diagnostic performance of miR-203, eligible studies were identified from biomedical databases. Based on these results, 11 studies were pooled and included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratios of miR-203 were 0.83 (95% confidence interval, CI: 0.78–0.86), 0.80 (95% CI: 0.77–0.83), and 19.27 (95% CI: 7.23–51.36) for the diagnosis of colorectal cancer. The area under the curve for miR-203 for diagnosing colorectal cancer was 0.89. Patients with higher expression of tissue miR-203 had poor overall survival (pooled hazard ratio: 1.63; 95% CI: 1.03–2.57, P=0.04), but serum miR-203 was not predictive (pooled hazard ratio: 1.59; 95% CI: 0.31–8.12, P=0.58). The miR-203 values of tissue and serum merged together may perhaps predict superior overall survival (pooled hazard ratio: 1.62; 95% CI: 0.93–2.82), but the effect was not significant (P=0.09).

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Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets

Cited by 55 publications

References 210 publications

Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways

Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

miR-203 as a novel biomarker for the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis

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