Overexpression of Pyruvate Carboxylase Is Correlated With Colorectal Cancer Progression and Supports Growth of Invasive Colon Cancer HT-29 Cell Line

2020 ◽  
Vol 40 (11) ◽  
pp. 6285-6293
Author(s):  
JARUNYA NGAMKHAM ◽  
CHANITRA THUWAJIT ◽  
PETI THUWAJIT ◽  
PEERAPAT KHAMWACHIRAPITHAK ◽  
KORNKAMON LERTSUWAN ◽  
...  
BMC Cancer ◽  
2009 ◽  
Vol 9 (1) ◽  
Author(s):  
Eira S Roth ◽  
David T Fetzer ◽  
Bruce J Barron ◽  
Usha A Joseph ◽  
Isis W Gayed ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5767
Author(s):  
Jarinyagon Chantawannakul ◽  
Paninnuch Chatpattanasiri ◽  
Vichugorn Wattayagorn ◽  
Mesayamas Kongsema ◽  
Tipanart Noikaew ◽  
...  

Colorectal cancer is one of the leading causes of cancer-related death in Thailand and many other countries. The standard practice for curing this cancer is surgery with an adjuvant chemotherapy treatment. However, the unfavorable side effects of chemotherapeutic drugs are undeniable. Recently, protein hydrolysates and anticancer peptides have become popular alternative options for colon cancer treatment. Therefore, we aimed to screen and select the anticancer peptide candidates from the in silico pepsin hydrolysate of a Cordyceps militaris (CM) proteome using machine-learning-based prediction servers for anticancer prediction, i.e., AntiCP, iACP, and MLACP. The selected CM-anticancer peptide candidates could be an alternative treatment or co-treatment agent for colorectal cancer, reducing the use of chemotherapeutic drugs. To ensure the anticancer properties, an in vitro assay was performed with “CM-biomimetic peptides” on the non-metastatic colon cancer cell line (HT-29). According to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results from peptide candidate treatments at 0–400 µM, the IC50 doses of the CM-biomimetic peptide with no toxic and cancer-cell-penetrating ability, original C. militaris biomimetic peptide (C-ori), against the HT-29 cell line were 114.9 µM at 72 hours. The effects of C-ori compared to the doxorubicin, a conventional chemotherapeutic drug for colon cancer treatment, and the combination effects of both the CM-anticancer peptide and doxorubicin were observed. The results showed that C-ori increased the overall efficiency in the combination treatment with doxorubicin. According to the acridine orange/propidium iodine (AO/PI) staining assay, C-ori can induce apoptosis in HT-29 cells significantly, confirmed by chromatin condensation, membrane blebbing, apoptotic bodies, and late apoptosis which were observed under a fluorescence microscope.


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.


2020 ◽  
pp. 1-6
Author(s):  
Alain Couvineau ◽  
S. Dayot ◽  
V. Gratio ◽  
P. Nicole ◽  
T. Voisin ◽  
...  

Colorectal cancer, which is the third most common cancer, is the main cause of digestive cancer death. Previous studies have demonstrated that orexins, hypothalamic neuropeptides involved in sleep and food intake regulations, have anti-tumoral properties in digestive cancers. In the present work, we investigated the anti-tumoral role of an orexin antagonist, almorexant, in colon cancer. The anti-tumoral role of almorexant has been determined by in vitro and in vivo studies using HT-29 colon cancer cell line, which expressed endogenous orexin receptor 1 subtype (OX1R). Our in vitro study indicated that almorexant was able to reduce HT-29 cell viability by induction of mitochondrial apoptosis involving the tyrosine phosphatase SHP2 and the p38 signaling pathways. In contrast, no effect was observed in the colon cancer cell line HCT-116, which does not express OX1R, demonstrating that the anti-tumoral effect of almorexant was mediated by OX1R. When HT-29 cells were xenografted in nude mice, the administration of almorexant strongly reduced the tumor development with a potency similar to orexin. Our study supports that almorexant, a small molecule analog of orexin peptide, could represent a putative candidate in the treatment of colorectal cancer.


2019 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Saeed Noorolyai ◽  
Behzad Baradaran

Background and Purpose: Colorectal cancer is the third leading cause of cancer death worldwide. MicroRNAs are a group of post-transcription regulators whose expression are altered in various cancers and affect the expression of different genes and contribute to cancer progression. According to studies, the expression of miR-193a-5p in some cancers, including colorectal cancer, is reduced. But so far, the main effects and mechanisms of miR-193a-5p in colorectal cancer are ambiguous and unknown. The purpose of this study was to investigate the effects of miR-193a-5p mimic transfection on HT-29 cell line and investigate the expression of vimentin molecule on these cells. Materials and Methods: First, the HT-29 cell line from colorectal cancer was cultured in RPMI-1640 culture media. Then, miR-193a-5p was transfected with Jet-PEI reagent and using the qRT-PCR technique, the expression of miR-193a-5p and vimentin gene was evaluated in miR-193a-5p transfected HT-29 cells and control group. Statistical analyzes were performed using GraphPad Prism 6 statistical software. Results: In this study, the simultaneous effect of miR-193a-5p mimic on HT-29 cells was investigated. Expression levels of miR-193a-5p was increased after transfection, and then, vimentin expression was altered, which was evaluated by using qRT-PCR. Conclusion: The results of this study revealed that miR-193a-5p may act as a tumor-suppressor by affecting the molecules such as vimentin. This microRNA has an important role in tumor metastasis. Therefore, it may be suggested as a potential therapeutic target in the treatment of colorectal cancer.


2021 ◽  
Vol 22 (14) ◽  
pp. 7260
Author(s):  
Umama Khan ◽  
Sabrina Chowdhury ◽  
Md Morsaline Billah ◽  
Kazi Mohammed Didarul Islam ◽  
Henrik Thorlacius ◽  
...  

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.


MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Jeyalakshmi Kandhavelu ◽  
Kumar Subramanian ◽  
Amber Khan ◽  
Aadilah Omar ◽  
Paul Ruff ◽  
...  

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fangfang Yang ◽  
Hua Wang ◽  
Bianbian Yan ◽  
Tong Li ◽  
Lulu Min ◽  
...  

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.


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.


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