scholarly journals Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour

RSC Advances ◽  
2017 ◽  
Vol 7 (82) ◽  
pp. 52039-52047 ◽  
Author(s):  
C. Dispenza ◽  
M. A. Sabatino ◽  
A. Ajovalasit ◽  
L. A. Ditta ◽  
M. Ragusa ◽  
...  

Soft nanogels, produced by electron beam irradiation, are conjugated to the inhibitor of miR-31, an important molecule in colorectal cancer progression. AntimiR-31 interacts with its biological target in vitro, without being detached from the nanogel.

Oncogenesis ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xin Huang ◽  
Yichao Hou ◽  
Xiaoling Weng ◽  
Wenjing Pang ◽  
Lidan Hou ◽  
...  

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.


2021 ◽  
Author(s):  
Chaofan Peng ◽  
Yuqian Tan ◽  
Peng Yang ◽  
Kangpeng Jin ◽  
Chuan Zhang ◽  
...  

Abstract BackgroundEmerging studies have investigated circRNAs as significant regulation factors in multiple cancer progression. Nevertheless, the biological functions and underlying mechanisms of circRNAs in colorectal cancer progression remain unclear.MethodsA novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of phenotype experiments in vitro and vivo were performed to investigate the role of circ-GALNT16 in CRC. FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were constructed to explore the molecular mechanisms of circ-GALNT16 in colorectal cancer.ResultsCirc-GALNT16 was downregulated in colorectal cancer and negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastasis ability of colorectal cancer in vitro and vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which resulted in the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. Furthermore, RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex.ConclusionsCirc-GALNT16 suppressed CRC progression via inhibiting Serpine1 expression through adjusting the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might work as a biomarker and therapeutic target for CRC.


2020 ◽  
Vol 40 (11) ◽  
pp. 6285-6293
Author(s):  
JARUNYA NGAMKHAM ◽  
CHANITRA THUWAJIT ◽  
PETI THUWAJIT ◽  
PEERAPAT KHAMWACHIRAPITHAK ◽  
KORNKAMON LERTSUWAN ◽  
...  

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Hong-li Jiao ◽  
Bin-shu Weng ◽  
Shan-shan Yan ◽  
Zi-mo Lin ◽  
Shu-yang Wang ◽  
...  

AbstractOxysterol-binding protein like protein 3 (OSBPL3) has been shown involving in the development of several human cancers. However, the relationship between OSBPL3 and colorectal cancer (CRC), particularly the role of OSBPL3 in the proliferation, invasion and metastasis of CRC remains unclear. In this study, we investigated the role of OSBPL3 in CRC and found that its expression was significantly higher in CRC tissues than that in normal tissues. In addition, high expression of OSBPL3 was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of OSBPL3 promoted the proliferation, invasion and metastasis of CRC in vitro and in vivo models. Moreover, we revealed that OSBPL3 promoted CRC progression through activation of RAS signaling pathway. Furthermore, we demonstrated that hypoxia induced factor 1 (HIF-1A) can regulate the expression of OSBPL3 via binding to the hypoxia response element (HRE) in the promoter of OSBPL3. In summary, Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. This novel mechanism provides a comprehensive understanding of both OSBPL3 and the RAS signaling pathway in the progression of CRC and indicates that the HIF1A–OSBPL3–RAS axis is a potential target for early therapeutic intervention in CRC progression.


2019 ◽  
Vol 20 (23) ◽  
pp. 6051 ◽  
Author(s):  
Miroslav Machala ◽  
Jiřina Procházková ◽  
Jiřina Hofmanová ◽  
Lucie Králiková ◽  
Josef Slavík ◽  
...  

The development and progression of colon cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.


2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Longci Sun ◽  
Hanbing Xue ◽  
Chunhui Jiang ◽  
Hong Zhou ◽  
Lei Gu ◽  
...  

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.


Author(s):  
Xinyang Lu ◽  
Zhiqiang Liu ◽  
Xiaofei Ning ◽  
Lunhua Huang ◽  
Biao Jiang

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xuemei Tang ◽  
Haoyu Ruan ◽  
Liu Dong ◽  
Sihan Li ◽  
Zhiyuan Wu ◽  
...  

lncRNA is a key epigenetic regulator in biological processes. In the human cancer transcriptome library MiTranscriptome, we identified GAU1 as the top upregulated lncRNA in colorectal cancer (CRC) by sample set enrichment analysis (overexpression ranking percentile = 99.75 %, P < 10 − 50 ), which is coexpressed with the potential oncogene GALNT8 (Spearman rho = 0.67 , P = 2.44 × 10 − 23 , TCGA dataset n = 184 ). Experimental data revealed that GAU1 regulates the expression of GALNT8. The overexpression of either GAU1 or GALNT8 significantly promotes the cell cycle and proliferation of CRC cell lines and correlates with poor prognosis in patients with CRC ( P = 3.04 × 10 − 2 ), while silencing of GAU1 or GALNT8 suppressed the cancer cell proliferation and induced the CRC cell line resistance to oxaliplatin in vitro treatment. Our results suggested that the previously less studied GAU1 and GALNT8 may play as CRC prognosis markers and potential targets for chemotherapy treatment.


2020 ◽  
Vol 528 ◽  
pp. 146583
Author(s):  
Hui Zhu ◽  
Kai Zheng ◽  
Dagang Guo ◽  
Hang Zang ◽  
Sen Yu ◽  
...  

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