scholarly journals Loss of cyclin A2 in murine colonic epithelial cells disrupts colon homeostasis by triggering DNA damage and dysplasia and high cyclin A2 expression is a good-prognosis factor in patients with colorectal cancer

2019 ◽  
Author(s):  
Yuchen Guo ◽  
Monica Gabola ◽  
Rossano Lattanzio ◽  
Conception Paul ◽  
Valérie Pinet ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Epithelial Cells ◽  
Meta Analysis ◽  
Good Prognosis ◽  
Prognosis Factor ◽  
Colonic Epithelial Cells ◽  
Tumor Subtypes ◽  
Cyclin A2 ◽  
Abnormal Mitoses

AbstractTo clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC) we generated mice deficient for cyclin A2 in colonic epithelial cells (CEC). Colons of those mice displayed architectural changes in the mucosa, and signs of inflammation as well as an increased proliferation of CEC associated with the appearance of low- and high-grade dysplasia. The main initial events triggering those alterations in cyclin A2 deficient CEC appear to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CEC promoted the development of dysplasia and adenocarcinomas in the murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein level and found higher expression in tumors of stage I and II patients compared to those of stage III and IV. A meta-analysis of 11 transcriptome datasets comprising 2,239 primary CRC tumors displayed differentCCNA2(the mRNA coding for cyclin A2) expression levels among the CRC tumor subtypes with highest in CMS1 and lowest in CMS4. Moreover, high expression ofCCNA2was found to be a good prognosis factor independently from other prognostic factors for the CMS1, CMS3 and CMS4 subtypes.

scholarly journals Targeting of Nrf2 induces DNA damage signaling and protects colonic epithelial cells from ionizing radiation

2012 ◽  
Vol 109 (43) ◽  
pp. E2949-E2955 ◽  
Author(s):  
S. B. Kim ◽  
R. K. Pandita ◽  
U. Eskiocak ◽  
P. Ly ◽  
A. Kaisani ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Ionizing Radiation ◽  
Colonic Epithelial Cells ◽  
Dna Damage Signaling

scholarly journals Hydroxyphenyl Butanone Induces Cell Cycle Arrest through Inhibition of GSK3β in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Songyan Zhang ◽  
Yunfeng Wang ◽  
Haopeng Zhang ◽  
Chengming Sun ◽  
Shuwei Dang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Tumor Cells ◽  
Colony Formation ◽  
Colorectal Cancer Cell Line ◽  
Colonic Epithelial Cells ◽  
Low Concentration ◽  
Key Factor

Background. Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. Methods. Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown. Results. Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. Conclusion. This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

scholarly journals Circular RNA hsa_circ_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling

2020 ◽  
Author(s):  
CHI LI ◽  
Hong Zhou
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Quantitative Polymerase Chain Reaction ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Colonic Epithelial Cells ◽  
Cycle Arrest

Abstract Background: In our study, has_circ_102209 was the most upregulated gene in colorectal cancer (CRC) tissues according to circRNA array data. The levels of hsa_circ_102209 in CRC specimens and cells, as well as its effects on CRC cells were investigated. Methods: The expression of hsa_circ_102209 in CRC and paired non-cancerous samples, human CRC and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circ_102209 knockdown were established using lentiviral vectors . Cell proliferative ability was evaluated using CCK-8 assay; cell migration and invasion were assessed by wound healing and Transwell assay. Cell cycle arrest and apoptosis were determined; apoptosis and EMT markers were examined using RT-qPCR and western blotting. Tumour development and levels of associated proteins were determined in hsa_circ_102209 knockdown mice. Results: Our results revealed that expression of hsa_circ_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (p<0.05). Additionally, the levels of hsa_circ_102209 was associated with tumor stage and occurrence of liver metastasis in CRC patients, and the expression of hsa_circ_102209 and miR-761 were negatively correlated (p<0.05). Moreover, hsa_circ_102209 was upregulated in CRC cell s compared with normal colonic epithelial cells. Knockdown of hsa_circ_102209 notably inhibited the proliferation, migration, invasion and EMT of CRC cell s (p<0.05), whereas enhanced cell cycle arrest at G0/G1 phase and apoptosis (p<0.05). Furthermore, miR-761/ Ras and Rab interactor 1 ( RIN1) axis was the putative target of hsa_circ_102209 in CRC and involved in hsa_circ_102209 -modulated growth and metastasis in CRC cell s (p<0.05). Knockdown of hsa_circ_102209 also remarkably suppressed tumor growth in vivo (p<0.05). Conclusions: our data revealed that the expression of hsa_circ_102209 was elevated in CRC samples and cells. Furthermore, hsa_circ_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circ_102209 /miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients .

scholarly journals Circular RNA hsa_circ_102209 promotes the growth and metastasis of colorectal cancer through miR-761-mediated Ras and Rab interactor 1 signaling

2020 ◽  
Author(s):  
CHI LI ◽  
Hong Zhou
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Quantitative Polymerase Chain Reaction ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Colonic Epithelial Cells ◽  
Cycle Arrest

Abstract Background: The levels of hsa_circ_102209 in colorectal cancer (CRC) specimens and cells, as well as its effects on CRC cells were investigated. Methods: The expression of hsa_circ_102209 in CRC and paired non-cancerous samples, human CRC and normal colonic epithelial cells were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cells with hsa_circ_102209 knockdown were established using lentiviral vectors. Cell proliferative ability was evaluated using CCK-8 assay; cell migration and invasion were assessed by wound healing and Transwell assay. Cell cycle arrest and apoptosis were determined; apoptosis and EMT markers were examined using RT-qPCR and western blotting. Tumour development and levels of associated proteins were determined in hsa_circ_102209 knockdown mice. Results: Our results revealed that expression of hsa_circ_102209 was remarkably increased in CRC tissues, where the levels of miR-761 were notably reduced (p<0.05). Additionally, the levels of hsa_circ_102209 was associated with histology grade and occurrence of liver metastasis in CRC patients, and the expression of hsa_circ_102209 and miR-761 were negatively correlated (p<0.05). Moreover, hsa_circ_102209 was upregulated in CRC cells compared with normal colonic epithelial cells. Knockdown of hsa_circ_102209 notably inhibited the proliferation, migration, invasion and EMT of CRC cells (p<0.05), whereas enhanced cell cycle arrest at G0/G1 phase and apoptosis (p<0.05). Furthermore, miR-761/Ras and Rab interactor 1 (RIN1) axis was the putative target of hsa_circ_102209 in CRC and involved in hsa_circ_102209-modulated growth and metastasis in CRC cells (p<0.05). Knockdown of hsa_circ_102209 also remarkably suppressed tumor growth in vivo (p<0.05). Conclusions: our data revealed that the expression of hsa_circ_102209 was elevated in CRC samples and cells. Furthermore, hsa_circ_102209 could promote the progression of CRC through miR-761/RIN1 axis. More importantly, hsa_circ_102209/miR-761/RIN1 signaling may be a novel therapeutic target for the treatment of CRC patients.

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