scholarly journals DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1767 ◽  
Author(s):  
Marta Jiménez-Martínez ◽  
Cristina M. Ostalé ◽  
Lennart R. van der Burg ◽  
Javier Galán-Martínez ◽  
James C. H. Hardwick ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Tumor Stage ◽  
Cell Contact ◽  
Epithelial Tumor ◽  
Dual Specificity ◽  
High Tumor Stage ◽  
Colorectal Cancer Progression

Cell contact inhibition (CCI) is deregulated in cancer. Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. We found that dual-specificity phosphatase 10 (DUSP10) is involved in CRC. DUSP10 overexpression increased the growth of CRC cell lines and mouse xenografts, while the opposite phenotype was observed by DUSP10 silencing. High cell density (HD) induced DUSP10 expression in CRC cell lines, particularly within the nucleus. Yes-associated protein 1 (YAP1) is activated by dephosphorylation, controlling organ growth and CCI, both processes being deregulated in CRC. Expression levels and localization of DUSP10 matched with YAP1 levels in CRC cell lines. DUSP10 and YAP1 co-immunoprecipitated and their interaction was dependent on YAP1 Ser397. The existence of DUSP10 and YAP1 pathway in vivo was confirmed by using a transgenic Drosophila model. Finally, in CRC patients’ samples, high levels of nuclear DUSP10 correlated with nuclear YAP1 in epithelial tumor tissue. Strong nuclear DUSP10 staining also correlated with high tumor stage and poor survival. Overall, these findings describe a DUSP10–YAP1 molecular link in CRC cell lines promoting cell growth in HD. We present evidence suggesting a pro-tumorigenic role of nuclear DUSP10 expression in CRC patients.

scholarly journals Knockdown of lncRNA CCAT1 Inhibits the Progression of Colorectal Cancer via hsa-miR-4679 Mediating the Downregulation of GNG10

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ning Wang ◽  
Jun Li ◽  
Ju He ◽  
Yong-Guang Jing ◽  
Wei-dong Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Proliferating Cells ◽  
Guanine Nucleotide Binding Protein ◽  
Colorectal Cell ◽  
Guanine Nucleotide Binding ◽  
Colorectal Cancer Progression

Great concerns have raised crucial roles of long noncoding RNAs (lncRNAs) on colorectal cancer progression due to the increasing number of studies in cancer development. Previous studies reveal that lncRNA CCAT1 plays an important role in the progression of a variety of cancers. However, the role of lncRNA CCAT1 in colorectal cancer is still unclear. In this study, we found that in both colorectal tissues and cell lines the level of lncRNA CCAT1 was increased. Downregulation of lncRNA CCAT1 inhibited the proliferation, migration, and invasion of colorectal cell lines and promoted apoptosis. We then found that hsa-miR-4679 could bind to lncRNA CCAT1 directly, and with further functional analyses, we confirmed that lncRNA CCAT1 sponged hsa-miR-4679 to promote the progression of colorectal cancer. Next, we found that hsa-miR-4679 was directly bound to 3 ′ UTR of GNG10 (guanine nucleotide-binding protein, gamma 10). GNG10 overexpression promoted the progression of colorectal cancer, and this phenotype could be reversed by miR-4679 mimics. At last, we knocked down CCAT1 in vivo and found that sh-CCAT1 reduced the tumor size and the number of proliferating cells. In summary, our findings revealed that lncRNA CCAT1 facilitated colorectal cancer progression via the hsa-miR-4679/GNG10 axis and provided new potential therapeutic targets for colorectal cancer.

scholarly journals Diethyldithiocarbamate-copper complex (CuET) inhibits colorectal cancer progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis-mediated aerobic glycolysis pathway

Oncogenesis ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xin Huang ◽  
Yichao Hou ◽  
Xiaoling Weng ◽  
Wenjing Pang ◽  
Lidan Hou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Copper Complex ◽  
Aerobic Glycolysis ◽  
Active Role ◽  
Downstream Effector ◽  
Glycolysis Pathway ◽  
Colorectal Cancer Progression

AbstractExploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer role in CRC. In this study, we found that CuET had a marked effect on suppressing CRC progression both in vitro and in vivo by reducing glucose metabolism. Mechanistically, using RNA-seq analysis, we identified ALDH1A3 as a target gene of CuET, which promoted cell viability and the capacity of clonal formation and inhibited apoptosis in CRC cells. MicroRNA (miR)-16-5p and 15b-5p were shown to synergistically regulate ALDH1A3, which was negatively correlated with both of them and inversely correlated with the survival of CRC patients. Notably, using co-immunoprecipitation followed with mass spectrometry assays, we identified PKM2 as a direct downstream effector of ALDH1A3 that stabilized PKM2 by reducing ubiquitination. Taken together, we disclose that CuET treatment plays an active role in inhibiting CRC progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis–mediated aerobic glycolysis pathway.

scholarly journals miR551b Regulates Colorectal Cancer Progression by Targeting the ZEB1 Signaling Axis

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 735 ◽  
Author(s):  
Kwang Seock Kim ◽  
Dongjun Jeong ◽  
Ita Novita Sari ◽  
Yoseph Toni Wijaya ◽  
Nayoung Jun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Normal Tissues

Our current understanding of the role of microRNA 551b (miR551b) in the progression of colorectal cancer (CRC) remains limited. Here, studies using both ectopic expression of miR551b and miR551b mimics revealed that miR551b exerts a tumor suppressive effect in CRC cells. Specifically, miR551b was significantly downregulated in both patient-derived CRC tissues and CRC cell lines compared to normal tissues and non-cancer cell lines. Also, miR551b significantly inhibited the motility of CRC cells in vitro, including migration, invasion, and wound healing rates, but did not affect cell proliferation. Mechanistically, miR551b targets and inhibits the expression of ZEB1 (Zinc finger E-box-binding homeobox 1), resulting in the dysregulation of EMT (epithelial-mesenchymal transition) signatures. More importantly, miR551b overexpression was found to reduce the tumor size in a xenograft model of CRC cells in vivo. Furthermore, bioinformatic analyses showed that miR551b expression levels were markedly downregulated in the advanced-stage CRC tissues compared to normal tissues, and ZEB1 was associated with the disease progression in CRC patients. Our findings indicated that miR551b could serve as a potential diagnostic biomarker and could be utilized to improve the therapeutic outcomes of CRC patients.

scholarly journals LncRNA DQ786243 contributes to proliferation and metastasis of colorectal cancer both in vitro and in vivo

2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Longci Sun ◽  
Hanbing Xue ◽  
Chunhui Jiang ◽  
Hong Zhou ◽  
Lei Gu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Proliferation And Metastasis ◽  
Non Coding Rnas ◽  
Colorectal Cancer Progression

This article aims to find the key long non-coding RNAs (LncRNAs) associated with colorectal cancer (CRC) and to study its biological functions in colorectal cancer progression. Our study has shown that upregulated LncRNA DQ786243 can regulate cell proliferation, cell cycle progression, cell apoptosis, migration, and invasion in CRC cells. Xenograft experiments confirmed that the growth of xenograft tumors formed by CRC cells was suppressed after silencing LncRNA DQ786243 expression. In conclusion, our study suggests that LncRNA DQ786243 is an oncogene that promotes tumor progression and leads us to propose that LncRNAs may serve as key regulatory hubs in CRC progression.

scholarly journals The Long Noncoding RNA HOTAIR Promotes Colorectal Cancer Progression by Sponging miR-197

2018 ◽  
Vol 26 (3) ◽  
pp. 473-481 ◽  
Author(s):  
Xinyang Lu ◽  
Zhiqiang Liu ◽  
Xiaofei Ning ◽  
Lunhua Huang ◽  
Biao Jiang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Downstream Target ◽  
Potential Applications ◽  
Colorectal Cancer Progression

The long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been found to be overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well known, evidence suggests that microRNA-197 (miR-197) might be involved in this event. In the present study, the significance of HOTAIR and miR-197 in the progression of colorectal cancer was detected in vitro and in vivo. We found that HOTAIR expression was significantly increased in colorectal cancer cells and tissues. In contrast, the expression of miR-197 was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation, migration, and invasion in vitro and in vivo. Moreover, HOTAIR modulated the progression of colorectal cancer by competitively binding miR-197. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of colorectal cancer.

scholarly journals UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition

2019 ◽  
Vol 8 (4) ◽  
pp. 560 ◽  
Author(s):  
Javier Martinez-Useros ◽  
Nuria Garcia-Carbonero ◽  
Weiyao Li ◽  
Maria J. Fernandez-Aceñero ◽  
Ion Cristobal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Progression

CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.

scholarly journals CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression

Oncogenesis ◽  
2021 ◽  
Vol 10 (12) ◽  
Author(s):  
Qing Liao ◽  
Yun Ren ◽  
Yuyi Yang ◽  
Xiaohui Zhu ◽  
Yunfei Zhi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Clinical Intervention ◽  
Underlying Mechanism ◽  
Invasion And Metastasis ◽  
Colorectal Cancer Progression ◽  
Chaperone Complex

AbstractLIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.

scholarly journals Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

2020 ◽  
Author(s):  
Takashi Nishina ◽  
Yutaka Deguchi ◽  
Wakami Takeda ◽  
Masato Ohtsuka ◽  
Daisuke Ohshima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Human Cancer ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Reporter Mice ◽  
Stat3 Phosphorylation ◽  
Colorectal Cancer Progression ◽  
Cancer And Inflammation

SUMMARYInterleukin (IL)-11 is a member of the IL-6 family of cytokines and involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells appeared in the colon of three murine tumor models, and a murine acute colitis model. Il11ra1 or Il11 deletion attenuated the development of colitis-associated colorectal cancer. IL-11+ cells expressed fibroblast markers, and genes associated with cell proliferation and tissue repair. IL-11 induced STAT3 phosphorylation in colonic fibroblasts, suggesting the activation of IL-11+ fibroblasts. Analysis using the human cancer database revealed that genes enriched in IL-11+ fibroblasts were elevated in human colorectal cancer, and correlated with reduced disease-free survival. Together, our results suggested that tumor cells induced IL-11+ fibroblasts, and that a feed-forward loop between IL-11 and IL-11+ fibroblasts might contribute to tumor development.

scholarly journals LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP

2020 ◽  
Author(s):  
Lin Hu ◽  
Jing Wang ◽  
Yunliang Wang ◽  
Linpeng Wu ◽  
Chao Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Colony Formation ◽  
Transcriptional Activity ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Migration And Invasion

Abstract Background: LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated. Methods: LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR. In vitro , colony formation, wound healing, migration and invasion assays were performed to investigate the effects of LOXL1 on cell proliferation, migration and invasion. In vivo , metastasis models and mouse xenografts were used to assess tumorigenicity and metastasis ability. Molecular biology experiments were utilized to reveal the underlying mechanisms by which LOXL1 modulates the Hippo pathway. Results: LOXL1 was highly expressed in normal colon tissues compared with cancer tissues. In vitro, silencing LOXL1 in CRC cell lines dramatically enhanced migration, invasion, and colony formation, while overexpression of LOXL1 exerted the opposite effects. The results of the in vivo experiments demonstrated that the overexpression of LOXL1 in CRC cell lines drastically inhibited metastatic progression and tumour growth. Mechanistically, LOXL1 inhibited the transcriptional activity of Yes-associated protein (YAP) by interacting with MST1/2 and increasing the phosphorylation of MST1/2. Conclusions: LOXL1 may function as an important tumour suppressor in regulating tumour growth, invasion and metastasis via negative regulation of YAP activity.

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