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 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 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 .

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 Patrinia scabiosaefolia inhibits the proliferation of colorectal cancer in vitro and in vivo via G1/S cell cycle arrest

2014 ◽  
Vol 33 (2) ◽  
pp. 856-860 ◽  
Author(s):  
MINGYUE ZHANG ◽  
GUODONG SUN ◽  
ALING SHEN ◽  
LIYA LIU ◽  
JINGZHEN DING ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Patrinia Scabiosaefolia

scholarly journals Berberine and Evodiamine Synergically Exert Anti-colorectal Cancer Effeccts via P38/MAPK/MAPKAPK2/HSP27 Signaling Pathway

2022 ◽  
Author(s):  
Ningning Chen ◽  
Yifang Jiang ◽  
Yi Yang ◽  
Ziyi Zhao ◽  
Chong Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Natural Products ◽  
Cell Cycle Arrest ◽  
P38 Mapk ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Cycle Arrest

Abstract Objective: Combinatorial natural products have high application potential for treatment of complex diseases owing to their synergistic effects and multi-targeting effect. However, studies have not explored the therapeutic effect and the synergetic mechanisms of action combinations of natural products. The present study aimed sought to evaluate the synergistic antitumor effects of a combination of Berberine and Evodiamine, and explore the drug effect on proliferation, migration, invasion of HCT116 and RKO human colorectal cancer cells. Results: The effect of berberine and evodiamine at a specific paired dose (BER30μM, EVO 0.8μM) was explored. A combination of berberine and evodiamine had no effect on activity and proliferation of HCT116 and RKO cells. The combination regulates the cell cycle of HCT116 and RKO cells at different cell phases. Berberine mainly blocked the cell cycle at G0/G1 phase, whereas evodiamine induced cell cycle arrest at G2/M phase. The results showed that the combined effect of berberine and evodiamine does not offset each other, but plays a synergistic role in regulation of colon cancer cell cycle. Western blot analysis showed that the combination of berberine and evodiamine regulated cell cycle by downregulating expression of cdc25c and upregulating expression of p21. The combination significantly inhibited cell migration and invasion by regulating EMT related proteins, upregulating expression of E-cadherin and downregulating expression of N-cadherin. The combination of berberine and evodiamine significantly inhibited phosphorylation of P38 MAPK in HCT116 and RKO cells, and further inhibited phosphorylation of the downstream MAPKAPK2 and HSP27, thus playing a synergistic anti-colon cancer role.Conclusion: Berberine and Evodiamine exhibit synergistic antitumor effects by suppressing cell proliferation, inducing cell cycle arrest and inhibiting EMT by modulating P38MAPK /MAPKAPK2/HSP27 pathway.Significance of the study: To illustrate the potential mechanism of formula-based combination of natural products, and explore the potential applications of the combination and possible antitumor therapeutic targets.

scholarly journals Novel hybrids derived from aspirin and chalcones potently suppress colorectal cancer in vitro and in vivo

MedChemComm ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 1722-1732 ◽  
Author(s):  
Shan Lu ◽  
Obinna N. Obianom ◽  
Yong Ai
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Proliferative Activity ◽  
Cycle Arrest

Novel hybrids derived from aspirin and chalcones were designed and synthesized. 7h had potent and selective anti-proliferative activity against CRC cells in vitro. 7h induced cell cycle arrest and apoptosis in CRC cells. 7h significantly inhibited the growth of implanted CRC cancer in mice.

scholarly journals Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

2020 ◽  
Author(s):  
zhongli wang ◽  
chao liu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Akt Signaling ◽  
Gastric Epithelial Cells ◽  
Akt Signaling Pathway ◽  
Potential Therapeutic Target ◽  
Cycle Arrest

Abstract Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice.Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p<0.05), while the levels of PI3K were notably increased (p<0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p<0.05), where circRNA_100269 and PI3K was inversely correlated (p<0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p<0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p<0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p<0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p<0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.

Celastrol inhibits the proliferation and induces apoptosis of colorectal cancer cells via downregulating NF-κB/COX-2 signaling pathways

2021 ◽  
Vol 21 ◽  
Author(s):  
Hua Zhang ◽  
Xiaojin Zhao ◽  
Fajun Shang ◽  
Huan Sun ◽  
Xu Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
The World ◽  
Cox 2

Background: Colorectal cancer (CRC) is the third-ranked malignant tumor in the world that contributes to the death of a major population of the world. Celastrol, a bioactive natural product isolated from the medicinal plant Tripterygium wilfordii Hook F, has been proved to be an effective anti-tumor inhibitor for multiple tumors. Objective: To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells. Methods: CCK-8 and clonogenic assay were used to analyze the cell proliferation in CRC cells. Flow cytometry analysis was conducted to assess the cell cycle and cell apoptosis. Wound-healing and cell invasion assay were used to evaluate the migrating and invasion capability of CRC cells. The potential antitumor mechanism of celastrol was investigated by qPCR, western blot, and confocal immunofluorescence analyses. Results: Celastrol effectively inhibited CRC cell proliferation by activating caspase-dependent cell apoptosis and facilitating G1 cell cycle arrest in a dose-dependent manner, as well as cell migration and invasion by downregulating the MMP2 and MMP9. Mechanistic protein expression revealed that celastrol suppressed the expression of COX-2 by inhibiting the phosphorylation of NF-κB p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby inhibiting its nuclear translocation and transcription activities. Conclusion: These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-κB/COX-2 pathway, leading to the inhibition of cell proliferation characterized by cell cycle arrest and caspase-dependent apoptosis, providing a potential alternative therapeutic agent for CRC patients.

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