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.

Silencing of Proteasome 26S Subunit ATPase 2 Regulates Colorectal Cancer Cell Proliferation, Apoptosis, and Migration

Chemotherapy ◽  
2019 ◽  
Vol 64 (3) ◽  
pp. 146-154 ◽  
Author(s):  
Jinghu He ◽  
Junjie Xing ◽  
Xiaohong Yang ◽  
Chenxin Zhang ◽  
Yixiang Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Survival Rate ◽  
Colony Formation ◽  
Cellular Level ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Proteasome 26S

Objective: Colorectal cancer (CRC) remains a major cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 2 (PSMC2) plays vital roles in regulating cell cycle and transcription and has been confirmed to be a gene potentially associated with some human tumors. However, the expression correlation and molecular mechanism of PSMC2 in CRC are still unclear. This study aimed to investigate the role of PSMC2 in malignant behaviors in CRC. Methods: The high protein levels of PSMC2 in CRC samples were identified by tissue microarray analysis. Lentivirus was used to silence PSMC2 in HCT116 and RKO cells; MTT and colony formation assay were performed to determine cell proliferation. Wound healing and Transwell assay were used to detect cell migration and invasion. Flow cytometry assay was applied to detect cell cycle and apoptosis. Result: The results showed that, among the 96 CRC patients, the expression of PSMC2 was a positive correlation with the clinicopathological features of the patients with CRC. Furthermore, the low PSMC2 expression group showed a higher survival rate than the high PSMC2 expression group. The expression levels of PSMC2 in cancer tissue were dramatically upregulated compared with adjacent normal tissues. In vitro, shPSMC2 was designed to inhibit the expression of PSMC2 in CRC cells. Compared with shCtrl, silencing of PSMC2 significantly suppressed cell proliferation, decreased single cell colony formation, enhanced apoptosis, and accelerated G2 phase and/or S phase arrest. Conclusion: Survival analysis indicated that high expression of PSMC2 in the CRC samples was associated with poorer survival rate than low expression of PSMC2, while the anti-tumor effect of PSMC2 silencing was also confirmed at the cellular level in vitro. Our results suggested that PSMC2 potentially worked as a regulator for CRC, and the silencing of PSMC2 may be a therapeutic strategy for CRC.

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.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals ZIC1 Is a Putative Tumor Suppressor in Thyroid Cancer by Modulating Major Signaling Pathways and Transcription Factor FOXO3a

2014 ◽  
Vol 99 (7) ◽  
pp. E1163-E1172 ◽  
Author(s):  
Wei Qiang ◽  
Yuan Zhao ◽  
Qi Yang ◽  
Wei Liu ◽  
Haixia Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Colony Formation ◽  
Promoter Hypermethylation ◽  
Migration And Invasion ◽  
Thyroid Cancer Cells

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

PGM1 Suppresses Colorectal Cancer Cell Migration And Invasion by Regulating PI3K/ AKT Pathway

2021 ◽  
Author(s):  
Zhewen Zheng ◽  
Xue Zhang ◽  
Jian Bai ◽  
Long Long ◽  
Di Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colony Formation ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Cycle Arrest ◽  
Cancer Pathogenesis

Abstract BackgroundPhosphoglucomutase 1(PGM1) is known for its involvement in cancer pathogenesis. However, its biological role in colorectal cancer (CRC) is unknown. Here, we studied the functions and mechanisms of PGM1 in CRC.Methods We verified PGM-1 as a DEG by a comprehensive strategy of the TCGA-COAD dataset mining and computational biology. Relative levels of PGM-1 in CRC tumors and adjoining peritumoral tissue were identified by qRT-PCR, WB, and IHC staining in a tissue microarray. PGM1 functions were analyzed using CCK8, EdU, colony formation, cell cycle, apoptosis, and Transwell migration and invasion assays. The influence of PGM1 was further investigated using tumor formation in vivo.ResultsPGM1 mRNA and protein were both reduced in CRC and the reduction was related to CRC pathology and overall survival. PGM1 knockdown stimulated both proliferation and colony formation, promoting cell cycle arrest and apoptosis while overexpression has opposite effects in CRC cells both in vivo and in vitro. Furthermore, we lined the actions of PGM1 to the PI3K/ AKT pathway. ConclusionWe verified that PGM1 suppresses CRC through the PI3K/ AKT pathway. These results suggest the potential for targeting PGM1 in CRC therapies.

scholarly journals FGF9/FGFR2 increase cell proliferation by activating ERK 1/2, Rb/E2F1, and cell cycle pathways in mouse Leydig tumor cells

2018 ◽  
Vol 109 (11) ◽  
pp. 3503-3518 ◽  
Author(s):  
Ming‐Min Chang ◽  
Meng‐Shao Lai ◽  
Siou‐Ying Hong ◽  
Bo‐Syong Pan ◽  
Hsin Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Cells ◽  
Leydig Tumor Cells
Sign in / Sign up

Export Citation Format

Share Document