Apobec-1 transcription in rat colon cancer: decreased apobec-1 protein production through alterations in polysome distribution and mRNA translation associated with upstream AUGs

Author(s):  
Shrikant Anant ◽  
Debnath Mukhopadhyay ◽  
Ken-Ichi Hirano ◽  
Thomas A. Brasitus ◽  
Nicholas O. Davidson
Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1438
Author(s):  
Sabeeta Kapoor ◽  
Trace Gustafson ◽  
Mutian Zhang ◽  
Ying-Shiuan Chen ◽  
Jia Li ◽  
...  

There is growing evidence that DNA repair factors have clinical value for cancer treatment. Nucleotide excision repair (NER) proteins, including excision repair cross-complementation group 2 (ERCC2), play a critical role in maintaining genome integrity. Here, we examined ERCC2 expression following epigenetic combination drug treatment. Attention was drawn to ERCC2 for three reasons. First, from online databases, colorectal cancer (CRC) patients exhibited significantly reduced survival when ERCC2 was overexpressed in colon tumors. Second, ERCC2 was the most highly downregulated RNA transcript in human colon cancer cells and rat tumors after treatment with the histone deacetylase 3 (HDAC3) inhibitor sulforaphane (SFN) plus JQ1, which is an inhibitor of the bromodomain and extraterminal domain (BET) family. Third, as reported here, RNA-sequencing of polyposis in rat colon (Pirc) polyps following treatment of rats with JQ1 plus 6-methylsulfinylhexyl isothiocyanate (6-SFN) identified Ercc2 as the most highly downregulated gene. The current work also defined promising second-generation epigenetic drug combinations with enhanced synergy and efficacy, especially in metastasis-lineage colon cancer cells cultured as 3D spheroids and xenografts. This investigation adds to the growing interest in combination approaches that target epigenetic ‘readers’, ‘writers’, and ‘erasers’ that are deregulated in cancer and other pathologies, providing new avenues for precision oncology and cancer interception.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Meseret Fesseha ◽  
Mee Young Hong

Abstract Objectives Colon Cancer is the second deadliest cancerous disease worldwide among men and women. It has been estimated that more than half of colon cancers may be preventable by dietary intervention. A disturbance of the homeostasis between cellular proliferation and apoptosis is associated with colon cancer development. Watermelon (Citrullus lanatus) is rich in L-citrulline, a precursor of L-arginine. It has been shown that L-arginine may have anti-inflammatory roles and serves as a substrate for synthesis of nitric oxide, which in turn exerts wide-ranging physiological effects including tumoricidal effects via modification of cell kinetics. Our research examined if colon cancer can be prevented with the supplementation of watermelon powder by lowering cellular proliferation but enhancing apoptosis. Methods In order to test the hypothesis, 21-days old 32 Sprague Dawley rats were allocated to three groups; control, L- arginine (0.36% L-arginine) and watermelon powder (0.5%, w/w). Carcinogen azoxymethane was injected at week 4 and 5, and colon tissues were harvested at 5 week after the 2nd carcinogen injection. Cell proliferation and apoptosis were enumerated using a quantitative immunohistochemical analysis of Ki-67 antibody and TUNEL assay, respectively. Results Cell proliferation was mainly located bottom of colonic crypt (P < 0.05). Apoptotic cells were mostly located in the upper part of crypt (P < 0.05). L-arginine and watermelon fed rats lowered cell proliferation index and proliferative zone (P < 0.05). However, no difference was found on apoptosis among the three groups. Conclusions These results suggest that watermelon powder supplementation may reduce the risk of colon cancer by reducing cell proliferation rather than alteration of apoptosis. Further study will follow to determine the mechanism of anti-proliferative effect of watermelon supplementation. Funding Sources National Watermelon Promotion Board; SDSU/UCSD Cancer Center Partnership Scholars Program.


2020 ◽  
Vol 12 (6) ◽  
pp. 403-409 ◽  
Author(s):  
Dieter A Wolf ◽  
Yingying Lin ◽  
Haoran Duan ◽  
Yabin Cheng

Abstract Studies over the past three years have substantially expanded the involvements of eukaryotic initiation factor 3 (eIF3) in messenger RNA (mRNA) translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination, and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting, and degradation. At the same time, eIF3 subunits appear to have specific functions that probably vary between different tissues and individual cells. Considering the broad functions of eIF3 in protein homeostasis, it comes as little surprise that eIF3 is increasingly implicated in major human diseases and first attempts at therapeutically targeting eIF3 have been undertaken. Much remains to be learned, however, about subunit- and tissue-specific functions of eIF3 in protein synthesis and disease and their regulation by environmental conditions and post-translational modifications.


1999 ◽  
Vol 90 (11) ◽  
pp. 1212-1217 ◽  
Author(s):  
Katsunao Nakagami ◽  
Tsutomu Uchida ◽  
Susumu Ohwada ◽  
Yukio Koibuchi ◽  
Yasuo Morishita

Author(s):  
Dieter A. Wolf ◽  
Yingying Lin ◽  
Haoran Duan ◽  
Yabin Cheng

Studies over the past three years have substantially expanded the involvements of eIF3 in mRNA translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting, and degradation. At the same time, eIF3 subunits appear to have specific functions that probably vary between different tissues and individual cells. Considering the broad functions of eIF3 in protein homeostasis, it comes as little surprise that eIF3 is increasingly implicated in major human diseases and first attempts at therapeutically targeting eIF3 have been undertaken. Much remains to be learned, however, about subunit- and tissue-specific functions of eIF3 in protein synthesis and disease and their regulation by environmental conditions and posttranslational modifications.


1990 ◽  
Vol 43 (4) ◽  
pp. 577-582
Author(s):  
J Songjie ◽  
Y Saito ◽  
T Muto ◽  
T Masaki ◽  
Y Morioka

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