Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line

Manoochehri, Hamed; Afshar, Saeid; Pashaki, Abdolazim Sedighi; Mahdavinezhad, Ali; Nikzad, Safoora; Najafi, Rezvan; Amini, Razieh; Gholami, Mohammad Hadi; Khoshghadam, Alireza; Saidijam, Massoud

doi:10.1007/s11604-017-0679-y

Cited by 46 publications

(29 citation statements)

References 59 publications

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“…It is known that the radioresistance of CRC cells leads to the failure of radiotherapy and toxic impacts of ionizing radiation [20]. Recent evidence has already demonstrated that miRNAs played an important role in radio-induced apoptosis and the radioresistance of CRC cells [21].…”

Section: Discussionmentioning

confidence: 99%

Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3

Chen

Liu

Zhang

et al. 2020

J Exp Clin Cancer Res

101

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Background: Cancer-associated fibroblasts (CAFs) have been intensively studied in recent studies with aims of finding more concrete evidence on their mechanism of involvement in tumor progression, which is currently unknown. CAFs can secrete exosomes which are loaded with proteins, lipids and RNAs, all of which affect tumor microenvironment. The present study identified microRNA-93-5p (miR-93-5p) as a novel exosomal cargo responsible for the pro-tumorigenic effects of CAFs on colorectal cancer (CRC). Methods: CAFs and normal fibroblasts (NFs) were isolated from cancerous tissues and matched with paracancerous tissues that had been surgically resected from CRC patients. The interaction among miR-93-5p, forkhead box A1 (FOXA1) and TGFB3 was identified through ChIP and dual luciferase reporter assays. The proliferation and apoptosis of SW480 cells co-cultured with CAFs-derived exosomes under irradiation were evaluated by CCK-8, colony formation, and flow cytometric assays. Tumorigenesis of SW480 cells in nude mice was assessed under the irradiation. Results: FOXA1 was found to be associated with reduced radioresistance in CRC cells and was verified as a target of miR-93-5p. CAFs-derived exosomes contained higher miR-93-5p than those from NFs, which augmented SW480 cell proliferation and rescued them from radiation-induced apoptosis. miR-93-5p was identified as a mediator of the exosomal effects of CAFs on SW480 cells, possibly through downregulating FOXA1 and upregulating TGFB3. FOXA1 could bind to the promoter of TGFB3, thereby inhibiting nuclear accumulation of TGFB3. Also, CAFs-derived exosomes containing miR-93-5p increased the tumor growth of SW480 cells in irradiated nude mice. Conclusion: The present study identifies miR-93-5p as a specific exosomal cargo that rescues CRC cells against radiation-induced apoptosis.

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Section: Discussionmentioning

confidence: 99%

Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3

Chen

Liu

Zhang

et al. 2020

J Exp Clin Cancer Res

101

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“…49 Impairing both miR-155 and miR-200c activities favored epithelium-to-mesenchyme transition and decreased the sensibility to gefitinib of these cell lines in particular by inducing epigenetic modifications. 49 MiR-155 was further shown to induce radioresistance of colorectal cancer cells, by targeting FOXO3a transcripts, 50 and in nasopharyngeal carcinoma tissues, by targeting Ubiquilin 1 transcripts and increasing PI3K and phospho-AKT activity. 51 High levels of miR-155 in contrast enhanced the sensitivity of triple-negative breast cancer cells to irradiation.…”

Section: Dual Roles Of Mir-155 In Cancermentioning

confidence: 99%

“…MiR‐155 was further shown to induce radioresistance of colorectal cancer cells, by targeting FOXO3a transcripts, and in nasopharyngeal carcinoma tissues, by targeting Ubiquilin 1 transcripts and increasing PI3K and phospho‐AKT activity . High levels of miR‐155 in contrast enhanced the sensitivity of triple‐negative breast cancer cells to irradiation.…”

Section: Dual Roles Of Mir‐155 In Cancermentioning

confidence: 99%

miR‐155expression in antitumor immunity: The higher the better?

Michaille

Awad

Fortman

et al. 2019

Genes Chromosomes & Cancer

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MicroRNAs are small noncoding RNAs that modulate gene expression either directly, by impairing the stability and/or translation of transcripts that contain their specific target sequence, or indirectly through the targeting of transcripts that encode transcription factors, factors implicated in signal transduction pathways, or epigenetic regulators. Abnormal expression of micro‐RNAs has been found in nearly all types of pathologies, including cancers. MiR‐155 has been the first microRNA to be implicated in the regulation of the innate and adaptative immune responses, and its expression is either increased or decreased in a variety of liquid and solid malignancies. In this review, we examine the oncogenic and antitumor potentials of miR‐155, with special emphasize on its dose‐dependent effects. We describe the impact of miR‐155 levels on antitumor activity of lymphocytes and myeloid cells. We discuss miR‐155 dose‐dependent effects in leukemias and analyze results showing that miR‐155 intermediate levels tend to be detrimental, whereas high levels of miR‐155 expression usually prove beneficial. We also examine the beneficial effects of high levels of miR‐155 expression in solid tumors. We discuss the possible causal involvement of miR‐155 in leukemias and dementia in individuals with Down's syndrome. We finally propose that increasing miR‐155 levels in immune cells might increase the efficiency of newly developed cancer immunotherapies, due to miR‐155 ability to target transcripts encoding immune checkpoints such as cytotoxic T lymphocyte antigen‐4 or programmed death‐ligand 1.

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“…Notably, miR-155 was widely studied as an oncogene involved in multiple cancers [8][9][10][11][12]. Recently, several studies showed that aberrant expression of miR-155 was tied to the diagnosis and prognosis of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis

et al. 2019

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Background: Recently, a growing number of studies have reported the coorelation between miR-155 and the diagnosis and prognosis of lung cancer, but results of these researches were still controversial due to insufficient sample size. Thus, we carried out the systematic review and meta-analysis to figure out whether miR-155 could be a screening tool in the detection and prognosis of lung cancer. Methods: A meta-analysis of 13 articles with 19 studies was performed by retrieving the PubMed, Embase and Web of Science. We screened all correlated literaters until December 1st, 2018. For the diagnosis analysis of miR-155 in lung cancer, sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve (AUC) were pooled to evaluate the accuracy of miRNA-155 in the diagnosis of lung cancer. For the prognosis analysis of miR-155 in lung cancer, the pooled HRs and 95% CIs of miR-155 for overall survival/disease free survival/progression-free survival (OS/DFS/PFS) were calculated. In addition, Subgroup and meta-regression analyses were performed to distinguish the potential sources of heterogeneity between studies. Results: For the diagnostic analysis of miR-155 in lung cancer, the pooled SEN and SPE were 0.82 (95% CI: 0.72-0.88) and 0.78 (95% CI: 0.71-0.84), respectively. Besides, the pooled PLR was 3.75 (95% CI: 2.76-5.10), NLR was 0.23 (95% CI: 0.15-0.37), DOR was 15.99 (95% CI: 8.11-31.52) and AUC was 0.87 (95% CI: 0.84-0.90), indicating a significant value of miR-155 in the lung cancer detection. For the prognostic analysis of miR-155 in lung cancer, upregulated miRNA-155 expression was not significantly associated with a poor OS (pooled HR = 1.26, 95% CI: 0.66-2.40) or DFS/PFS (pooled HR = 1.28, 95% CI: 0.82-1.97). Conclusions: The present meta-analysis demonstrated that miR-155 could be a potential biomarker for the detection of lung cancer but not an effective biomarker for predicting the outcomes of lung cancer. Furthermore, more well-designed researches with larger cohorts were warranted to confirm the value of miR-155 for the diagnosis and prognosis of lung cancer.

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Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line

Abstract: These observations indicate that miR-222 and miR-155 could induce radiation resistance in colorectal cancer by targeting PTEN and FOXO3a genes, respectively. Therefore, miR-222 and miR-155 can be suggested as good biomarkers of CRC radiation response.

Cited by 46 publications

References 59 publications

Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3

Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3

miR‐155expression in antitumor immunity: The higher the better?

The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis

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