PRMT3 promotes tumorigenesis by methylating and stabilizing HIF1α in colorectal cancer

AbstractAbnormal angiogenesis occurs during the growth of solid tumors resulting in increased vascular permeability to fluids and metastatic cancer cells. Anti-angiogenesis therapy for solid tumors is effective in the treatment of cancer patients. However, the efficacy of anti-angiogenesis therapy is limited by drug resistance. The findings of the current study showed that HIF1α R282 is methylated by PRMT3, which is necessary for its stabilization and oncogene function. Analysis showed that PRMT3-mediated tumorigenesis is HIF1α methylation-dependent. A novel therapeutic molecule (MPG-peptide) was used to inhibit HIF1α expression. These findings provided information on PRMT3 signaling pathway and HIF1/VEGFA signaling pathway and offer a novel therapeutic strategy for colorectal cancer, mainly for treatment of anti-angiogenesis resistance patients.

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Upregulation lnc-NEAT1 contributes to colorectal cancer progression through sponging miR-486-5p and activating NR4A1/Wnt/β-catenin pathway

Cancer Biomarkers ◽

10.3233/cbm-201733 ◽

2020 ◽

pp. 1-11

Author(s):

Zhining Liu ◽

Yimei Gu ◽

Xiaohu Cheng ◽

Heng Jiang ◽

Yang Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Signaling Pathway ◽

Cancer Progression ◽

Luciferase Reporter ◽

Colorectal Cancer Cells ◽

Colorectal Cancer Progression ◽

Colorectal Cancer Patients ◽

Cancer Tissues

Colorectal cancer is a major public health problem and fourth guiding cause of cancer-induced mortality worldwide. The five-year survival rate for patients with colorectal cancer remains poor, and almost half of colorectal cancer patients present recurrence and die within five years. The increasing studies showed that long non-coding RNA (lncRNA) was involved in colorectal cancer. Therefore, this study was used to explore molecular mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in colorectal cancer. The real-time quantitative polymerase chain reaction (RT-qPCR) was employed to estimate the expression levels of NEAT1, Nuclear receptor 4 A1 (NR4A1), and miR-486-5p in colorectal cancer tissues and cells. Kaplan-Meier curve was conducted to analyze relationship between survival time of colorectal cancer patients and level of NEAT1. The protein levels of NR4A1, β-catenin, c-Myc, and cyclinD1 were assessed with western blot assay. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were performed to evaluate proliferation and apoptosis of colorectal cancer cells, respectively. The migration and invasion abilities of cells were examined by transwell assay. The relationship between miR-486-5p and NEAT1 or NR4A1 was confirmed by dual-luciferase reporter assay. We found NEAT1 and NR4A1 were highly expressed in colorectal cancer tissues and cell lines compared with controls. Loss-functional experiments revealed that knockdown of NEAT1 or NR4A1 repressed proliferation and motility, while inducing apoptosis of colorectal cancer cells. The gain of NR4A1 could abolish NEAT1 silencing-induced effects in colorectal cancer cells. In addition, NEAT1 contributed to colorectal cancer progression through mediating NR4A1/Wnt/β-catenin signaling pathway. In conclusion, NEAT1 stimulated colorectal cancer progression via acting as competing endogenous RNA to sponge miR-486-5p and regulate NR4A1/Wnt/β-catenin signaling pathway.

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Abstract 855: Targeting STAT3in vitroandin vivoreveals a novel therapeutic strategy to sensitize colorectal cancer cells to chemoradiotherapy

10.1158/1538-7445.am2014-855 ◽

2014 ◽

Author(s):

Melanie Spitzner ◽

Birte Roesler ◽

Christian Bielfeld ◽

Carolin Herzberg ◽

Georg Emons ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Therapeutic Strategy ◽

Colorectal Cancer Cells ◽

Novel Therapeutic

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Efficacy of Cancer Chemotherapy in Relation to the Pretreatment Number of Lymphocytes in Patients with Metastatic Solid Tumors

The International Journal of Biological Markers ◽

10.1177/172460080401900208 ◽

2004 ◽

Vol 19 (2) ◽

pp. 135-140 ◽

Cited By ~ 58

Author(s):

P. Lissoni ◽

F. Brivio ◽

L. Fumagalli ◽

G. Messina ◽

V. Ghezzi ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Lung Cancer ◽

Cancer Patients ◽

Solid Tumors ◽

Lymphocyte Count ◽

Metastatic Cancer ◽

Normal Lymphocyte ◽

Response To Chemotherapy ◽

Previously Treated

The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis in terms of survival in advanced cancer patients. This finding is not surprising because of the fundamental role of lymphocytes in mediating tumor cell destruction. Despite the importance of lymphocytes in the pathogenesis of cancer, there are only few data about the profile and the function of lymphocytes during the various antitumor therapies, and in particular the relation between lymphocyte pretreatment number and response to chemotherapy remains to be established. The present study was performed to evaluate whether the evidence of lymphocytopenia before the onset of treatment may influence the efficacy of chemotherapy in metastatic cancer patients affected by the most frequent tumor types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63; breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and folates in untreated colorectal cancer, weekly irinotecan in pretreated colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast cancer patients who had been previously treated with anthracyclines. Lymphocyte count was considered to be abnormally low for values below 1500/mm3. Lymphocytopenia was found in 79/183 (43%) patients, without any significant differences in relation to tumor histology. A complete response (CR) was achieved in 6/104 patients with a normal lymphocyte count and in none of the 79 lymphocytopenic patients. A partial response (PR) was obtained in 39 patients with a normal lymphocyte count and in only eight patients with a low lymphocyte count prior to therapy. Therefore, irrespective of the type of chemotherapy, the objective tumor response rate (CR + PR) in lymphocytopenic patients was significantly lower than in patients with normal pretreatment lymphocyte counts (8/79 vs 45/104; p<0. 001). This study shows that the evidence of lymphocytopenia prior to chemotherapy is associated with a lower efficacy of treatment in terms of objective tumor regression rates in patients with metastatic solid tumors, and suggests that the action of chemotherapy may depend at least in part on an interaction with the antitumor immunity. Pretreatment lymphocyte count may represent a new, simple biological marker to be taken into consideration by oncologists in the chemotherapeutic treatment of metastatic cancer.

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