Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner

Pathak, Surajit; Wei, Meng; Nandy, Suman Kumar; Ping, Jie; Bişgin, Atıl; Helmfors, Linda; Waldmann, Patrik; Sun, Xiaoying

doi:10.18632/oncotarget.5815

Cited by 49 publications

(33 citation statements)

References 87 publications

(77 reference statements)

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“…Notably, Pathak et al (45) reported that let-7f-5p was highly upregulated in the human colon cancer HCT116 and SN38 cell lines following radiation treatment in a p53-directed manner, indicating that let-7f-5p may contribute to the chemoresistance of CRC. However, the specific role of let-7f-5p in CRC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of let‑7f‑5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro‑apoptotic proteins

et al. 2018

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Abstract. Colorectal cancer (CRC) is one of the most frequently occurring primary malignant tumors worldwide. Chemotherapeutic resistance is a major clinical problem in the treatment of CRC. Therefore, it is of great importance to investigate novel biomarkers that may predict chemoresistance and facilitate the development of individualized treatment for patients with CRC. The present study reported that let-7f-5p expression was elevated in chemotherapy-resistant CRC tissues compared with chemotherapy-sensitive tissues. Furthermore, upregulating let-7f-5p increased the expression levels of the anti-apoptotic proteins, B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and decreased the activity of caspase-3 and caspase-9 in CRC cells. By contrast, downregulating let-7f-5p yielded the opposite effect. Notably, the results indicated that let-7f-5p promoted chemotherapeutic resistance by directly repressing the expression of several pro-apoptotic proteins, including tumor protein p53, tumor protein p53-inducible nuclear protein 1, tumor protein p53-inducible nuclear protein 2 and caspase-3. Therefore, a novel mechanism by which let-7f-5p enhances the resistance of CRC cells to chemotherapeutics has been revealed, indicating that silencing let-7f-5p may become an effective therapeutic strategy against CRC. IntroductionColorectal cancer (CRC) is one of the most prevalent causes of cancer-associated mortality worldwide (1,2). Clinically, 5-fluorouracil (5-FU)-based chemotherapy serves as the initial first-line chemotherapeutic drug of choice in patients with CRC; however, the response rates to 5-FU are ~15% in patients with advanced CRC (3). Although novel therapeutic approaches, including combination chemotherapy of 5-FU and oxaliplatin (FOLFOX) or irinotecan (FOLFIRI), have presented promising potential, the majority of the patients continue to exhibit inadequate responses (4,5). The failure of chemotherapy in CRC patients is primarily attributed to therapeutic resistance following a long period of treatment (6). These observations emphasize that chemotherapeutic resistance is a major obstacle in the treatment of CRC, and that the molecular mechanisms underlying this issue remain unclear.Chemotherapeutic resistance poses a major challenge in cancer chemotherapy. Chemoresistance of tumor cells develops primarily due to acquired resistance de novo, following an initially sensitive response, and/or in combination with pre-established cell-intrinsic mechanisms (7). A number of well-established mechanisms are reported to be involved in cancer drug resistance, including failure of the drug to reach or enter the target cell, formation of efflux pumps on the surface of tumor cells, increased expression of anti-apoptotic proteins, induction of drug-detoxifying mechanisms and upregulation of DNA repair enzymes (8,9). However, there is an absence of integral understanding of acquired drug resistance in the context of CRC. Such insight may be crucial for the

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Section: Discussionmentioning

confidence: 99%

Upregulation of let‑7f‑5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro‑apoptotic proteins

et al. 2018

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“…About 50% of patients with colon cancer will present with metastasis either at the time of diagnosis or develop distant relapses after therapy [3]. Current primary treatments of colon cancer include surgery, chemotherapy, and radiotherapy [4]. Chemical drugs targeting epidermal growth factor receptor (EGFR) and KRAS have been reported to significantly prolong the survival of CRC patients [5].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

Lü

Sheng

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Colon cancer is one of the most commonly diagnosed and deadly cancers worldwide. Further understanding of the biological mechanisms is important for exploring the molecular biomarkers and therapeutic targets of this disease. Dysregulation of long non-coding RNAs (lncRNAs) has been reported to be associated with the development and progression of various cancers. XIAP-AS1 is a novel lncRNA, which can regulate apoptosis in gastric cancer cells. However, the role of XIAP-AS1 in colorectal cancer (CRC) remains unclear. In this study, we found that XIAP-AS1 expression was significantly increased in CRC tissues and its expression showed a positive correlation with TNM stage and cumulative survival rate of CRC. To investigate whether XIAP-AS1 regulates the progression of CRC, we knocked down its expression in several CRC cell lines. CCK-8 assays showed that XIAP-AS1 knockdown remarkably suppressed CRC cell growth and arrested the cell cycle at the G0/G1 phase (flow cytometric analysis). Furthermore, XIAP-AS1 knockdown also remarkably blocked cell invasion of colon cancer cells by regulating the expression of EMT markers, such as E-cadherin, ZO-1, vimentin, and N-cadherin. Importantly, we found that XIAP-AS1 knockdown significantly reduced STAT3 phosphorylation. Overall, this study suggests that lncRNA XIAP-AS1 might serve as a potential oncogene for colon cancer.

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“…It also has been demonstrated that let-7f targeted A20, a feedback inhibitor of the NF-κB pathway, to modulate the immune response to mycobacterium tuberculosis infection [13], suggesting the tight relationship between let-7f and NF-κB pathway. In addition, bioinformatics analysis pointed out that the highly up-regulated miRNAs, including let-7f-5p miRNA, were correlated with colon cancer pathways and associated with cytokines expression, including IL-10 [14].…”

Section: Introductionmentioning

confidence: 99%

NF-κB/let-7f-5p/IL-10 pathway involves in wear particle-induced osteolysis by inducing M1 macrophage polarization

Gao

et al. 2018

Cell Cycle

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NF-κB signaling pathway shows significant influence on wear particle-induced osteolysis, and this study aims to explore the underlying mechanism and the role of let-7f-5p in this process. A mouse calvarial osteolysis model was constructed with PMMA particles, and the bone marrow-derived macrophages (BMMs) were isolated from the osteolysis area. The expression of miRNA and protein was determined by qRT-PCR and western blot, respectively. The level of cytokines was evaluated with ELISA. Recombinant plasmids were transfected into cells for the endogenous expression of related genes. Dual-luciferase reporter assay was performed to determine the interaction between let-7f-5p and IL-10 in macrophage RAW264.7 cells. M1 macrophage polarization and expression of let-7f-5p were promoted in BMMs of osteolysis mouse model, compared with that in sham group. The expression of let-7f-5p was increased in the process of M1 macrophage polarization that induced by PMMA. Let-7f-5p was involved in M1 polarization in macrophages that treated with PMMA. IL-10 was negatively regulated by let-7f-5p. NF-κB regulated the expression of IL-10 through let-7f-5p. NF-κB participated in the PMMA-induced M1 macrophage polarization through let-7f-5p. Let-7f-5p contributed to PMMA-induced osteolysis by promoting M1 polarization of macrophages. The NF-κB/let-7f-5p/IL-10 pathway induces M1 macrophage polarization, and thus contributing to wear particle-induced osteolysis.

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Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner

Cited by 49 publications

References 87 publications

Upregulation of let‑7f‑5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro‑apoptotic proteins

Upregulation of let‑7f‑5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro‑apoptotic proteins

RETRACTED ARTICLE: Long non-coding XIAP-AS1 regulates cell proliferation, invasion and cell cycle in colon cancer

NF-κB/let-7f-5p/IL-10 pathway involves in wear particle-induced osteolysis by inducing M1 macrophage polarization

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