TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer

Ntavatzikos, Anastasios; Spathis, Aris; Patapis, Paul; Machairas, Nikolaos; Vourli, Georgia; Peros, George; Papadopoulos, Iordanis N.; Panayiotides, Ioannis G.; Koumarianou, Anna

doi:10.4251/wjgo.v11.i7.551

Cited by 23 publications

(23 citation statements)

References 64 publications

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“…However, the blood metastasis, peritoneal metastasis and lymph node metastasis of colon cancer cells after surgery could cause the recurrence of colon cancer (Martínez-Meza et al 2019 ). The spread of cancer cells caused by blood metastasis was a crucial factor which affected the survival rate of colon cancer patients (Ntavatzikos et al 2019 ). Therefore, we urgently need to develop a new therapy to inhibit the metastasis and spread of colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

MTBP promoted the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2

Shayimu

Yusufu

Rehemutula

et al. 2021

Animal Cells and Systems

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Colon cancer is a malignant tumor that seriously affects human health. Recently, studies revealed that the expression of MTBP enhanced the proliferation and metastasis of many types of cancer cells. And the data also showed that MTBP has the potential to regulate the expression of ZEB2. However, it is unclear whether MTBP can affect the proliferation, migration and invasion of colon cancer cells by modulating the expression of ZEB2. In this study, we established the MTBP overexpression and knockdown colon cancer cells with the transfection. Next, CCK-8 and transwell assays were carried out to determine the changes of the proliferation and invasion of colon cancer cells, respectively. After that, we overexpressed the ZEB2 in these MTBP knockdown colon cancer cells. Finally, the invasion and migration of these cells were detected with the same methods. We revealed that overexpression of MTBP enhanced the proliferation and invasion of colon cancer cells. Moreover, suppression of MTBP repressed the proliferation, migration and invasion of colon cancer cells. Furthermore, MTBP promoted the expression of ZEB2. The overexpression of ZEB2 abolished the MTBP knockdown induced inhibition of the migration and invasion of colon cancer cells. These results implied that MTBP enhanced the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2.

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Section: Discussionmentioning

confidence: 99%

MTBP promoted the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2

Shayimu

Yusufu

Rehemutula

et al. 2021

Animal Cells and Systems

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“…In recent studies, 5-FU chemotherapy efficacy was found markedly reduced by 50% in patient cohort afflicted with 5′-UTR 2R/3G, 3C/3G, and 3G/3G polymorphisms, when compared to 5′-UTR 2R/2R, 2R/3C, and 3C/3C carriers [ 226 ]. While in separate studies, the loss of heterozygosity (LOH) was factored in as well, reporting lower risk of disease recurrence and death for patients with 2G/3G, 2G/LOH, and 3C/LOH genotypes [ 227 ]. Although no correlation between 3′-UTR polymorphism and 5-FU efficacy was found in the study conducted by Qihong Nie and colleague (2019), it was established by Ntavatzikos and colleagues (2019) that the presence of 3′-UTR ins/LOH is an independent indication for increased risk for disease relapse and death.…”

Section: Mechanism Of Resistance By Key 5-fluorouracil Enzymesmentioning

confidence: 99%

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Azwar

Seow

Abdullah

et al. 2021

Biology

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5-Fluorouracil (5-FU) plus leucovorin (LV) remain as the mainstay standard adjuvant chemotherapy treatment for early stage colon cancer, and the preferred first-line option for metastatic colon cancer patients in combination with oxaliplatin in FOLFOX, or irinotecan in FOLFIRI regimens. Despite treatment success to a certain extent, the incidence of chemotherapy failure attributed to chemotherapy resistance is still reported in many patients. This resistance, which can be defined by tumor tolerance against chemotherapy, either intrinsic or acquired, is primarily driven by the dysregulation of various components in distinct pathways. In recent years, it has been established that the incidence of 5-FU resistance, akin to multidrug resistance, can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery, regulation of autophagy, epithelial-to-mesenchymal transition, cancer stem cell involvement, tumor microenvironment interactions, miRNA dysregulations, epigenetic alterations, as well as redox imbalances. Certain resistance mechanisms that are 5-FU-specific have also been ascertained to include the upregulation of thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, and the downregulation of thymidine phosphorylase. Indeed, the successful modulation of these mechanisms have been the game plan of numerous studies that had employed small molecule inhibitors, plant-based small molecules, and non-coding RNA regulators to effectively reverse 5-FU resistance in colon cancer cells. It is hoped that these studies would provide fundamental knowledge to further our understanding prior developing novel drugs in the near future that would synergistically work with 5-FU to potentiate its antitumor effects and improve the patient’s overall survival.

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“…Hematogenous metastasis is the dominating cause of failure in the treatment of colon cancer. The survival rate of colon cancer is overtly relevant to clinical stage, and the 5-year survival rates of patients with no metastasis, local metastasis and distant metastasis are 90, 70 and 10%, respectively [5]. Therefore, to find the markers of early diagnosis and explore the key molecules involved in the growth and metastasis of colon cancer is the focus of current research.…”

Section: Introductionmentioning

confidence: 99%

LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway

Cheng

Rong

Zhou

et al. 2020

J Exp Clin Cancer Res

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Background: LncRNA LINC00662 is closely related to the occurrence and development of cancer. This study aims to explore the effect of LINC00662 on colon cancer tumor growth and metastasis and its molecular mechanism. Methods: CCK8, colony formation, transwell, scratch wound, TUNEL, flow cytometry, RT-PCR, western blotting and immunohistochemistry assays were used to detect the proliferation, apoptosis, invasion and migration of colon cancer cell and mRNA and protein expressions. Luciferase reporter and RNA pull down assays were used to detect the combination of LINC00662 and miR-340-5p or IL22 and the combination of miR-340-5p and CLDN8/IL22. Coimmunoprecipitation were used to detect the co-expression of CLDN8 and IL22 in colon cell lines. The targets of LINC00662 were predicated by Starbase v2.0. The target genes of miR-340-5p were predicated by miRDB and TargetScan. GO and KEGG enrichment analysis were performed by DAVID website. Results: LINC00662 was up-regulation in colon cancer tissues and cell lines. Univariate Cox regression analysis showed that the LINC00662 expression level was related to the poor prognosis. LINC00662-WT and miR-340-5p mimics co-transfection depressed luciferase activity and IL22/CLDN8-WT and miR-340-5p inhibitors co-transfection memorably motivated luciferase activity. LINC00662 overexpression promoted cell proliferation, invasion and migration, and inhibited cell apoptosis in colon cancer. In vivo xenograft studies in nude mice manifested that LINC00662 overexpression prominently accelerate tumor growth. There was an opposite reaction in the biological functions of colon cells and tumor growth between LINC00662 overexpression and LINC00662 inhibition in vitro and in vivo. The functions of miR-340-5p mimics regulating the biological functions of colon cells and tumor growth were consistent with those of LINC00662 inhibition. CLDN8 and IL22, as target genes of miR-340-5p, reversed the functions of LINC00662 affecting the biological functions of colon cells and the protein levels of Bax, Bcl-2, XIAP, VEGF, MMP-2, E-cadherin and N-cadherin. Co-immunoprecipitation experiments indicated that CLDN8 directly interact with IL22 in colon cell lines. LINC00662 regulated CLDN8 and IL22 expressions and the activation of ERK signaling pathway via targeting miR-340-5p. Conclusion: LINC00662 overexpression promoted the occurrence and development of colon cancer by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway.

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TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer

Cited by 23 publications

References 64 publications

MTBP promoted the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2

MTBP promoted the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway

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