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 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 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.

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

2020 ◽  
Vol 18 (1) ◽  
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. Graphical abstract

scholarly journals Exosome-transmitted circCOG2 promotes colorectal cancer progression via miR-1305/TGF-β2/SMAD3 pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lei Gao ◽  
Xiaolong Tang ◽  
Qingsi He ◽  
Guorui Sun ◽  
Chao Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Metastatic Potential ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Colorectal Cancer Progression ◽  
Dual Luciferase Reporter Assay

AbstractCircular RNAs (circRNA) are abundantly present in the exosome. Yet, the role of exosome-transmitted circRNA in colorectal cancer (CRC) remains unclear. In this study, we examined the function and mechanism of circCOG2 in CRC. We analyzed the expression of circCOG2 in CRC tissues, plasmas, and exosomes by qRT-PCR. The function of circCOG2 was evaluated by CCK-8, clone formation, transwell and wound healing assay, and using an in vivo study; while its mechanism was analyzed using a dual luciferase reporter assay, RNA pull-down assay, Western blot, and rescue experiments. We found that circCOG2 was increased in CRC tissues, plasmas, and exosomes. Upregulated circCOG2 promoted CRC proliferation, migration, and invasion through the miR-1305/TGF-β2/SMAD3 pathway, and this effect could be transmitted from CRC cells with the high metastatic potential to CRC cells with low metastatic potential by exosomes. Our results revealed that circCOG2 is correlated with poor prognosis and may be used as a therapeutic target for CRC.

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 Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fangfang Yang ◽  
Hua Wang ◽  
Bianbian Yan ◽  
Tong Li ◽  
Lulu Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Aberrant Expression ◽  
Cell Migration And Invasion ◽  
Lovo Cells ◽  
Colorectal Cancer Progression

Abstract The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTA3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3- knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR- 1301/STAT3 axis in CRC metastasis.

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 Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caihong Wen ◽  
Xiaoqing Feng ◽  
Honggang Yuan ◽  
Yong Gong ◽  
Guangsheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Pdcd4 Expression ◽  
Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

scholarly journals lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

2018 ◽  
Vol 26 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Jie Zhang ◽  
Xiao-Yan Li ◽  
Ping Hu ◽  
Yuan-Sheng Ding
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

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