Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells

Gao, Yuran; Zhi-cheng, Zhang; Li, Kai; Gong, Liying; Yang, Qingzhu; Huang, Xuemei; Hong, Chengcheng; Ding, Mei; Yang, Huanjie

doi:10.1038/cddis.2017.311

Cited by 76 publications

(62 citation statements)

References 44 publications

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“…Gemcitabine is the standard of care for PDAC, and several miRNAs have been described to be related to Gemcitabine response. miR-145, acting as sponge for the long intergenic ncRNAs (lincRNAs) linc-DYNC2H1-4, regulates EMT and CSC properties, impacting resistance to Gemcitabine in PDAC cells [130]. miR-205, a miRNA associated to CSC phenotypes in PDAC, is highly downregulated in Gemcitabine-resistant cells, and a reduction in CSCs, EMT and chemoresistance markers is observed when miR-205 is overexpressed, strongly suggesting that miR-205 re-sensitizes Gemcitabine-resistant PDAC cells to Gemcitabine [131].…”

Section: Role Of Mirnas In Cscsmentioning

confidence: 99%

The Epigenetic Landscape of Pancreatic Cancer Stem Cells

2018

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Data now indicates that in addition to genetic alterations/mutations, human cancer cells exhibit important changes in their epigenome. In the context of this review, we define the epigenome as the chemical compounds and/or proteins that can interact with nuclear DNA to direct the specific and localized activation or silencing of genes to control the production of cellular proteins (directly or indirectly) in a given cell. Our ever-growing knowledge of how the epigenome can affect cellular processes has largely changed our view of cancer being a solely genetic disease. Nowadays, cancer is largely defined and characterized by the dynamic changes in both the genome and epigenome, which function together and contribute concomitantly to cancer initiation and progression. Since epigenetic modifications are crucial processes involved in controlling cellular identity and lineage fate, perturbations in this layer of gene regulation can contribute to the acquisition of new cellular characteristics different than those that were "initially" intended. For example, aberrant epigenetic alterations may transform normal non-cancer cells into cancer stem cells (CSCs), endowing them with the loss of differentiation and the acquisition of stem-like characteristics. In this review, we will focus our discussion on CSCs in the context of pancreatic ductal adenocarcinoma (PDAC). We will discuss how different epigenetic modifications create a landscape that can impact CSC identity and the way this small sub-population of cells contributes to tumor initiation, progression, and resistance to therapy. Moreover, we will highlight the latest discoveries in epigenetic-based therapies as a means of targeting CSCs.

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Section: Role Of Mirnas In Cscsmentioning

confidence: 99%

The Epigenetic Landscape of Pancreatic Cancer Stem Cells

2018

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“…The underlying mechanisms of PDAC have been linked to long non-coding RNAs (lncRNAs) 2 , 3 . The discovery of lncRNAs has been one of the most unexpected findings of the genomics era and provides a promising avenue for gaining biological insights 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and migration of pancreatic ductal adenocarcinoma

Wang

Lü

et al. 2018

Cell Death Dis

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Long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). Previously, we found that melittin treatment suppressed PDAC tumor growth. However, it is unclear whether lncRNAs have any role in the melittin-induced suppression of PDAC. In this study, we used microarray data to identify 844 lncRNAs that were significantly differentially expressed in response to melittin treatment. Of these lncRNAs, we focused on the lncRNA NONHSAT105177, which had about a 22-fold increase in expression with melittin treatment. We found that melittin treatment increased NONHSAT105177 expression in PDAC cell lines but not in normal pancreatic ductal epithelial cell line. NONHSAT105177 expression was significantly lower in PDAC cancer tissues than in adjacent noncancerous tissues. Additionally, overexpression of NONHSAT105177 inhibited PDAC cell proliferation, migration, and the epithelial–mesenchymal transition (EMT), both in vitro and in vivo. Consistent with the mechanism of action of melittin, NONHSAT105177 significantly downregulated cholesterol pathway genes, including Clusterin (CLU). Moreover, we found that NONHSAT105177 trafficking was mediated by exosomes. The combined findings of our current and previous studies suggest that NONHSAT105177 mediated the melittin-induced inhibition of PDAC cell growth and metastasis, which indicated a potential target for developing new strategies.

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“…miRNAs have been reported as oncogenes or tumor suppressor genes, which regulate tumorigenesis and metastasis through targeting various genes that are abnormally expressed in cancer cells (11). As a tumor suppressive miRNA, miR-145 has been reported to be decreased in numerous types of human cancer, including pancreatic cancer (12), prostate cancer (13), cervical cancer (14), gastric cancer (15), oral cancer (16), colorectal cancer (17), breast cancer (18), bladder cancer (19) and melanoma (20). These previous studies have indicated that miR-145 may suppress the growth, migration and invasion of cancer cells, and inhibit tumorigenesis by targeting various genes that are abnormally expressed in tumors.…”

Section: Introductionmentioning

confidence: 99%

miR‑145 inhibits human non‑small-cell lung cancer growth by dual-targeting RIOK2 and NOB1

Chen

You

et al. 2018

Int J Oncol

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Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide. Right open reading frame kinase 2 (RIOK2) and nin one binding protein (NOB1) are important accessory factors in ribosome assembly. In our previous study, RIOK2 and NOB1 were revealed to be highly expressed in NSCLC, and were associated with the clinicopathological characteristics of patients with NSCLC, i.e. TNM clinical stage, lymph node metastasis and differentiation. In addition, RIOK2 expression was correlated with NOB1. To further explore the mechanism and the RIOK2 and NOB1 signaling pathway, microRNA (miR) regulation was analyzed. The tumor suppressor miR‑145 has been reported to be lowly expressed in numerous types of human cancer; in the present study, the expression levels of miR‑145 were decreased in patients with NSCLC. Furthermore, RIOK2 and NOB1 were predicted to be the direct targets of miR‑145 using bioinformatics software; this was further validated using a dual luciferase reporter assay. In addition, the protein expression levels of RIOK2 and NOB1 were inhibited in response to miR‑145 overexpression, thus resulting in the suppression of cell viability, migration and invasion. These results suggested that RIOK2 and NOB1 may be potential targets in the treatment of NSCLC, and miR‑145 may be considered a therapeutic inhibitor of both genes.

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Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells

Cited by 76 publications

References 44 publications

The Epigenetic Landscape of Pancreatic Cancer Stem Cells

The Epigenetic Landscape of Pancreatic Cancer Stem Cells

Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and migration of pancreatic ductal adenocarcinoma

miR‑145 inhibits human non‑small-cell lung cancer growth by dual-targeting RIOK2 and NOB1

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