Knockdown of Rhotekin 2 expression suppresses proliferation and induces apoptosis in colon cancer cells

Pang, Xiaoming; Li, Rui; Shi, Daren; Pan, Xudong; Ma, Chen; Zhang, Guangbo; Mu, Chuanyong; Chen, Weichang

doi:10.3892/ol.2017.7182

Cited by 19 publications

(22 citation statements)

References 14 publications

(22 reference statements)

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“…Furthermore, similar findings were reported in melanoma and, nasopharyngeal carcinoma as well as lung cancer ( 28 , 38 , 39 ). It is well-established that the balance between cell birth and cell death is important; once this balance is disrupted, tumor progression will occur ( 40 , 41 ). There may be other pathways or receptors associated with PD-L1 that have not yet been identified, which the effect of antitumor was stronger than the effect of PD-L1 leading to the evasion of tumor cells from host monitoring in tumor microenvironment, when PD-L1 is highly expressed.…”

Section: Discussionmentioning

confidence: 99%

Programmed death ligand 1 expression in esophageal cancer following definitive chemoradiotherapy: Prognostic significance and association with inflammatory biomarkers

Tang

et al. 2018

Oncol Lett

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Abstract.Immunotherapy with anti-programmed cell death protein 1 or programmed death ligand 1 (PD-L1) agents has demonstrated promising efficacy for the treatment of various types of malignancies. However, the role of PD-L1 as a tumor prognostic marker remains poorly understood. In the present study, the prognostic value of PD-L1 expression in esophageal carcinoma (EC) following definitive chemoradiotherapy (CRT) was investigated, and its associations with three systemic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were further explored. A total of 104 patients with non-metastatic EC, who underwent definitive CRT between January 2009 and December 2012, were retrospectively analyzed. The expression of PD-L1 was examined by immunohistochemistry and the impact of PD-L1 expression level on overall survival (OS) was assessed. Furthermore, pretreatment neutrophil, lymphocyte, platelet and monocyte counts were obtained from routine blood tests to calculate the NLR, PLR and LMR. PD-L1 was overexpressed in EC compared with normal esophageal epithelium, with a positive expression rate of 37.5%. Additionally, patients with positive PD-L1 expression had a lower NLR than those with negative PD-L1 expression (P= 0.001). On multivariate analysis, the positive staining of PD-L1 was significantly associated with improved OS (HR, 0.6; 95% CI, 0.372-0.965; P= 0.035). Kaplan-Meier survival analysis showed a similar result (P= 0.009). Additionally, sex (HR, 0.449; 95% CI, 0.229-0.880; P= 0.020), clinical stage III (HR, 2.471; 95% CI, 1.171-5.212; P=0.018), and receipt of concurrent chemoradiation (HR, 0.590; 95% CI, 0.368-0.945; P= 0.028) were all independent prognostic factors in EC treated with definitive CRT. The correlation of NLR with PD-L1 expression validated the relevance of immunity and inflammation. In summary, the present study demonstrated that positive PD-L1 expression is associated with improved survival in patients with EC treated with radical CRT, indicating that PD-L1 is a promising prognostic marker.

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Section: Discussionmentioning

confidence: 99%

Programmed death ligand 1 expression in esophageal cancer following definitive chemoradiotherapy: Prognostic significance and association with inflammatory biomarkers

Tang

et al. 2018

Oncol Lett

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“…Colon cancer is a frequently occurring gastrointestinal tumor, which is responsible for over 1 million newly diagnosed cases across the world per year [ 1 ]. Colon cancer has been regarded as the fourth most fatal cancer in the world, with a mortality rate of about 50% [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Wang

Guo²,

Zhou

et al. 2020

J Exp Clin Cancer Res

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Background Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer. Methods Tumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p. Results We found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497–5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro. Conclusions Our work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation.

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“…Colon cancer is a common malignant tumor of the in the gastrointestinal system that occurs in the colon, with the complications of intestinal obstruction and lower gastrointestinal bleeding [19]. As the characteristics of safety, minimal side effects and improved the quality of life, Chinese herbs are increasingly used as cancer-preventive drug for patients who prefer a conservative treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

Zhang¹,

Wang²,

Liu³

et al. 2020

Preprint

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Background: Colon cancer is increasing recently but the high cost and adverse side effects experienced always leads to treatment drop out. Zingiber officinale, commonly known as ginger, is a popular herbal medicine and this study was aimed to identify the active compounds from ginger and to investigate its anti-cancer mechanisms through network pharmacology construction. Results: Ginger compounds were discerned through the TCMSP, which were filtered by the metrics of oral bioavailability and drug likeness, and its related targets were searched. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. Six potential active compounds, 288 interacting targets in addition to 1356 disease-related targets were collected, of which 114 intersection targets were obtained. The PPI network showed that 32 targets including SRC, PIK3R1, and TP53 were identified as key targets. These targets were mainly associated with the biological processes like transmembrane receptor protein tyrosine kinase signaling pathway, regulation of cellular protein localization, cellular response to oxidative stress. KEGG enrichment manifested that ginger probably produced preventive effects against colon cancer by regulating significant signaling pathway like pathway in cancer, hepatitis B, and estrogen signaling pathway. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 could be viewed as the most potential target proteins, which were validated by molecular docking simulation.Conclusion: This study demonstrated the multi-component, multi-target, and multi-pathway characteristics of ginger, providing novel insight for ginger compounds developed as new drug for anti-colon cancer.

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Knockdown of Rhotekin 2 expression suppresses proliferation and induces apoptosis in colon cancer cells

Cited by 19 publications

References 14 publications

Programmed death ligand 1 expression in esophageal cancer following definitive chemoradiotherapy: Prognostic significance and association with inflammatory biomarkers

Programmed death ligand 1 expression in esophageal cancer following definitive chemoradiotherapy: Prognostic significance and association with inflammatory biomarkers

RETRACTED ARTICLE: NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

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