The dual role of mir-146a in metastasis and disease progression

Alipour, Shahriar; Shiva, Gholizadeh Ghaleh-aziz; Babaei, Ghader; Jeddi, Farhad; Hosein, Amjadi; Parsa, Haji

doi:10.1016/j.biopha.2020.110099

Cited by 33 publications

(17 citation statements)

References 46 publications

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“…These results suggest that this miRNA could stimulate the emergence and the growth of intrinsic hepatic progenitor cells. Previous reports have described several functions of miR-146a-5p , including the regulation of immune mechanisms [ 32 – 34 ], hepatic lipid and glucose metabolism [ 35 , 36 ], hepatocellular carcinoma behaviors [ 37 – 40 ], and cell stemness [ 41 ]. This miRNA also acts as a tumor suppressor to reduce the invasion and cancer cell migration of hepatocellular carcinoma [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers

et al. 2021

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Background Small hepatocyte-like progenitor cells (SHPCs) appear to form transient clusters in rat livers treated with retrorsine (Ret) and 70% partial hepatectomy (PH). We previously reported that the expansion of SHPCs was amplified in Ret/PH-treated rat livers transplanted with Thy1+ cells derived from d-galactosamine-treated injured livers. Extracellular vesicles (EVs) produced by hepatic Thy1+ donor cells activated SHPCs via interleukin (IL)-17 receptor B signaling. As bone marrow-derived mesenchymal cells (BM-MCs) also express Thy1, we aimed to determine whether BM-MCs could also promote the growth of SHPCs. Methods BM-MCs were isolated from dipeptidyl-peptidase IV (DPPIV)-positive rats. BM-MCs or BM-MC-derived EVs were administered to DPPIV-negative Ret/PH rat livers, and the growth and the characteristics of SHPC clusters were evaluated 14 days post-treatment. miRNA microarrays and cytokine arrays examined soluble factors within EVs. Small hepatocytes (SHs) isolated from an adult rat liver were used to identify factors enhancing hepatocytic progenitor cells growth. Results The recipient’s livers were enlarged at 2 weeks post-BM-MC transplantation. The number and the size of SHPCs increased remarkably in livers transplanted with BM-MCs. BM-MC-derived EVs also stimulated SHPC growth. Comprehensive analyses revealed that BM-MC-derived EVs contained miR-146a-5p, interleukin-6, and stem cell factor, which could enhance SHs’ proliferation. Administration of EVs derived from the miR-146a-5p-transfected BM-MCs to Ret/PH rat livers remarkably enhanced the expansion of SHPCs. Conclusions miR-146a-5p involved in EVs produced by BM-MCs may play a major role in accelerating liver regeneration by activating the intrinsic hepatocytic progenitor cells.

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Section: Discussionmentioning

confidence: 99%

Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers

et al. 2021

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“…This transcript was proven to promote migration and invasion in colorectal cancer [57]. miR-146a-5p proved to have a dual role in metastasis and disease progression [58]. In our patient cohort, it was found to be overexpressed in tumor tissue versus normal tissue in COAD.…”

Section: Discussionmentioning

confidence: 65%

Epithelial–Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma

Busuioc

Ciocan-Cârtiţă

Braicu

et al. 2021

JPM

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Colon adenocarcinoma (COAD) remains an important cause of cancer-related mortality worldwide. Epithelial–mesenchymal transition (EMT) is a key mechanism, promoting not only the invasive or metastatic phenotype but also resistance to therapy. Using bioinformatics approaches, we studied the alteration on EMT related genes and its implication on COAD prognostic based on public datasets. For the EMT mechanisms, two overexpressed genes were identified (NOX4 and IGF2BP3), as well as five downregulated genes (BMP5, DACT3, EEF1A2, GCNT2 and SFRP1) that were related to prognosis in COAD. A qRT-PCR validation step was conducted in a COAD patient cohort comprising of 29 tumor tissues and 29 normal adjacent tissues, endorsing the expression level for BMP5, as well as for two of the miRNAs targeting key EMT related genes, revealing upregulation of miR-27a-5p and miR-146a-5p. The EMT signature can be used to develop a panel of biomarkers for recurrence prediction in COAD patients, which may contribute to the improvement of risk stratification for the patients.

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“…While in cervical cancer and breast cancer CSCs, miR-146a-5p played a completely opposite role [14,34]. It has been indicated that the expression of miR-146a-5p in tumors was also related to chemoresistance and metastasis of tumor cells [56]. MiR-146a-5p could enhance the induction effect of platinum on apoptosis so as to prohibit cell proliferation in EOC cells [11,33].…”

Section: Discussionmentioning

confidence: 99%

“…The abnormal expression of miRNA-146a in CSCs has been found in many studies. And its effects in different tumors might be completely opposite [56]. As an exosomal miRNA in colorectal cancer, miR-146a-5p could target NUMB to activate wnt signaling pathway to generate and maintain cancer stem cells characteristics for promotion of tumor formation [7,26].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of cancer stem cells-associated lncRNA-miRNA-mRNA network for ovarian cancer via microarray and Gene Expression Omnibus database

Li¹,

Wang²,

Zhou³

2020

Preprint

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Background: Cancer stem cells (CSCs) are associated with the recurrence, metastasis and chemoresistance of epithelial ovarian cancer. Competing endogenous RNAs (CeRNAs) play an important role in maintenance of ovarian cancer stem cell-like cells (OCSCs) characteristics. To construct a ceRNA regulatory network for OCSCs, microarray technology and Gene Expression Omnibus (GEO) database had been used. Human serous epithelial ovarian carcinoma cell line COC1 cells were treated with cisplatin and paclitaxel then maintained in stem cell conditions for 6 days to obtain CD117+/CD133+ cells (OCSCs). We identified the differentially expressed miRNAs (DEMs), lncRNA (DELs) and mRNA (DEGs) between OCSCs and COC1 by microarray and combined them with representative microarray profiles in GEO Database. Results: According to the combination, 28 DEMs were identified at first, and 452 DEGs were obtained combining with the predicted targets of these miRNAs and our mRNA microarray results. Up-regulated DEGs of them were significantly enriched in ‘p53 signaling pathway’, ‘FoxO signaling pathway’ and ‘MicroRNAs in cancer’, whereas down-regulated DEGs were significantly enriched in ‘Adherens junction’ and ‘Hepatitis C’ pathway. 29 transcripts of 17 lncRNAs should be the ceRNAs of 10 of these miRNAs according to bioinformatics predicted results and lncRNA microarray. Finally, we obtained ceRNA network with 10 DEMs, 21 DEGs, and 25 transcripts of 13 DELs which should play an important role in maintenance of OCSCs characteristics. LINC00665-miR-146a-5p-NRP2 should be one of ceRNA pathways of the network. The qPCR results indicated that the expression of miR-146a-5p in OCSCs was lower than that in COC1, and LINC00665 shows the opposite trend. These results were consistent with the results of microarray partially. When LINC00665 expression was up-regulated in COC1, the cell proliferation ability enhanced, apoptosis rate reduced, and the percentage of G2/M phase cells increased. Conclusions: The ceRNA network we constructed may be involved in the stem cell characteristics maintenance of OCSCs and provide directions for further OCSCs research in the future, so as to assist the development and treatment of ovarian cancer.

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The dual role of mir-146a in metastasis and disease progression

Cited by 33 publications

References 46 publications

Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers

Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers

Epithelial–Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma

Integrated analysis of cancer stem cells-associated lncRNA-miRNA-mRNA network for ovarian cancer via microarray and Gene Expression Omnibus database

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