Downregulation of microRNA-132 by DNA hypermethylation is associated with cell invasion in colorectal cancer

Qin, Jun; Jin, Ke; Xu, Jiacheng; Wang, Feiran; Zhou, Youlang; Jiang, Yasu; Wang, Zhiwei

doi:10.2147/ott.s91560

Cited by 29 publications

(19 citation statements)

References 24 publications

(26 reference statements)

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“…The effects of miRNAs on cancer progression also depend on the function of the downstream targets that they suppress 29. Therefore, the targets of each miRNA need to be identified.…”

Section: Discussionmentioning

confidence: 99%

Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1

Zhang¹,

Fu²,

Pan³

et al. 2016

OTT

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MicroRNAs (miRNAs) play an important role in cancer development and progression, altering several biological functions by affecting targets through either degradation of mRNAs or suppression of protein translation. One such miRNA, miR-1247, is downregulated in various cancers, but its biological role in non-small-cell lung cancer (NSCLC) is unknown. This study found that the expression of miR-1247 was significantly reduced in NSCLC cell lines and tumor tissues compared with matched normal lung tissues and cell lines as a result of DNA hypermethylation. Overexpression of miR-1247 or demethylation by 5-azacytidine (5-Aza) treatment dramatically inhibited cell growth, migration, invasion, and cell cycle progression. Furthermore, Stathmin 1 (STMN1) was found to be an immediate and functional target of miR-1247. The expression of STMN1 was significantly increased in NSCLC cell lines but was decreased by 5-Aza treatment. In addition, miR-1247 upregulation partially inhibited STMN1-induced promotion of migration and invasion of A549 and H1299 cells. The results suggest that miR-1247 was silenced by DNA methylation. MiR-1247 and its downstream target gene STMN1 may therefore be a future target for the treatment of NSCLC.

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“…The effects of miRNAs on cancer progression also depend on the function of the downstream targets that they suppress 29. Therefore, the targets of each miRNA need to be identified.…”

Section: Discussionmentioning

confidence: 99%

Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1

Zhang¹,

Fu²,

Pan³

et al. 2016

OTT

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“…Emerging evidence shows that dysregulation of miRNAs plays a vital role in many biological processes, including proliferation, invasion and apoptosis (18). Hyper-methylation and reduced expression of anti-tumorigenic miRNAs’ promoters are associated with cancer progression in colorectal (19), chronic lymphocytic leukemia (20), cervical (21), breast (22), and gastric cancers (17,23). On the other hand, hypo-methylation of pro-oncogenic miRNAs’ promoters have been reported in hepatocellular carcinoma (24), pancreatic (25), and ERα positive breast cancers (26).…”

Section: Introductionmentioning

confidence: 99%

Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells

Shao

Chen

Peng

et al. 2018

Molecular Cancer Research

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The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, the regulation and role of miR-196b-5p in gastric cancer was investigated. Quantitative real-time RT-PCR (qPCR) demonstrated that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P<0.01). In addition, it was determined that HOXA10, a homeobox family member and host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P<0.001). Quantitative pyrosequencing methylation analysis, demonstrated significantly lower levels of DNA methylation at the HOXA10 promoter in gastric cancer, as compared to non-neoplastic gastric mucosa specimens. 5-Aza-2′-deoxycytidine treatment confirmed that demethylation of HOXA10 promoter induces the expression of HOXA10 and miR-196b-5p in gastric cancer cell model systems. Using the Tff1-KO mouse model of gastric neoplasia, hypo-methylation and overexpression of HOXA10 and miR-196b-5p in gastric tumors was observed, as compared to normal gastric mucosa from Tff1-WT mice. Mechanistically, reconstitution of TFF1 in human gastric cancer cells lead to an increased HOXA10 promoter methylation with reduced expression of HOXA10 and miR-196b-5p. Functionally, miR-196b-5p reconstitution promoted human gastric cancer cell proliferation and invasion in vitro. In summary, the current data demonstrates overexpression of miR-196b-5p in gastric cancer and suggests that TFF1 plays an important role in suppressing the expression of miR-196b-5p by mediating DNA methylation of the HOXA10 promoter. Loss of TFF1 expression may promote proliferation and invasion of gastric cancer cells through induction of promoter hypo-methylation and expression of the HOXA10/miR-196b-5p axis.

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“…Paxillin and tensin 3 mRNA and protein levels were reduced in macrophages upon coculture with breast cancer cells, as well as after treatment with miR-375 containing supernatants from apoptotic MCF-7 cells. Paxillin is a focal adhesion adapter protein that, depending on its subcellular localization, can positively or negatively regulate cell migration [147][148][149]. Similarly, tensin 3 acts as a link between the extracellular matrix and the cytoskeleton and functionally contributes to the switch between adhesive and non-adhesive states in cancer cells, including breast cancer [150,151].…”

Section: Guo Et Al Investigated Mechanisms Of Breast Cancer Invasionmentioning

confidence: 99%

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

Syed

Frank

Raue

et al. 2019

Cells

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MicroRNAs (miRs) significantly contribute to the regulation of gene expression, by virtue of their ability to interact with a broad, yet specific set of target genes. MiRs are produced and released by almost every cell type and play an important role in horizontal gene regulation in the tumor microenvironment (TME). In the TME, both tumor and stroma cells cross-communicate via diverse factors including miRs, which are taking central stage as a therapeutic target of anti-tumor therapy. One of the immune escape strategies adopted by tumor cells is to release miRs as a Trojan horse to hijack circulating or tumor-localized monocytes/macrophages to tune them for pro-tumoral functions. On the other hand, macrophage-derived miRs exert anti-tumor functions. The transfer of miRs from host to recipient cells depends on the supramolecular structure and composition of miR carriers, which determine the distinct uptake mechanism by recipient cells. In this review, we provide a recent update on the miR-mediated crosstalk between tumor cells and macrophages and their mode of uptake in the TME.(TNF-α), and provoke the secretion of pro-inflammatory cytokines including interleukin-1 (IL-1), IL-6, IL-12, IL-23, and TNF-α and reactive nitrogen and oxygen intermediates (RNI, ROI) [5]. In contrast, anti-inflammatory stimuli such as IL-4, IL-13, IL-10, and glucocorticoid or immune complexes (IC) plus LPS induce macrophages to an M2 phenotype. This type is characterized by a decreased production of pro-inflammatory cytokines, increased production of anti-inflammatory cytokines (e.g., IL-10), and factors that mediate immunosuppression and tissue remodeling. M2 macrophages have been divided into further subgroups. The M2a type is generated in response to IL-3 and IL-13, while M2b macrophages respond to immune complexes and Toll-like receptor (TLR) activation. M2c macrophages represent deactivated macrophages that suppress pro-inflammatory cytokines, while the M2d type represents a regulatory macrophage [6] that is often grouped with TAMs [5,7,8]. In line with these varied responses, Janus-faced macrophage functions are largely determined by their microenvironment rather than their genetic imprint [9,10]. In tumors and during the resolution of inflammation, hijacked macrophages attain pro-tumor or wound healing phenotypes due to tumor-derived factors [11], which emerge as a target for tumor therapy [12,13]. TAMs expressing classical activation markers produce pro-inflammatory cytokines and reactive oxygen species (ROS) and, thus, are crucial for tumor cell killing [14,15]. The high degree of plasticity demonstrated by macrophages in pathological conditions can be attributed to a) dynamic regulation of gene expression and b) rapid activation of signaling cascades that determine their effector functions. Signaling cascades triggered by local environmental cues and controlling the transcriptional machinery, ultimately determine the effector functions of macrophages in the tumor microenvironment (TME). Hence, understanding and modulating these ...

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Downregulation of microRNA-132 by DNA hypermethylation is associated with cell invasion in colorectal cancer

Cited by 29 publications

References 24 publications

Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1

Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1

Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

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