MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer

Ye, Gengtai; Huang, Kai; Yu, Jiang; Zhao, Liying; Zhu, Xuejun; Yang, Qingbin; Li, Wende; Jiang, Yuming; Zhuang, Baoxiong; Liu, Hao; Shen, Zhiyong; Da, Wang; Li, Yan; Zhang, Lei; Zhou, Huixia; Hu, Yanfeng; Deng, Haijun; Li, Guoxin; Qi, Xiaolong

doi:10.7150/thno.20512

Cited by 75 publications

(79 citation statements)

References 46 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Herein, we found that circRHOBTB3 contained the binding sites of miR-654-3p predicted by bioinformatic website circinteractome and verified there was direct binding relationship between circRHOBTB3 and miR-654-3p using biotinylated-nucleic probe pull down assay and luciferase reporter experiments, which suggested that circRHOBTB3 might serve as a sponge for miR-654-3p to inhibit the proliferation of GC. MiRNAs have been shown to be a large family of gene regulator that negatively regulate their target mRNAs in a sequence-specific manner and its role in cancers have been extensively studied [31,42,43]. Numerous evidences have confirmed that miRNAs play essential roles in multiple biological process related to cancer, including cell differentiation, proliferation, tumorigenesis, angiogenesis, invasion, and metastasis [44,45].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggested that circRNAs mainly function as miRNA sponge to sequester miRNA and then regulate subsequent gene expression [30,31]. To investigate whether circRHOBTB3 served as "miRNA sponge" in GC cells, we selected the eleven top potential binding miRNA (miR-244, miR-494, miR-548p, miR-570, miR-586, miR-600-3p, miR-619-3p, miR-654-3p, miR-1200-5p, miR-1265-5p, miR-1305) with a context score percent-ile≥90 predicted by CircInteractome database.…”

Section: Circrhobtb3 Acted As a Molecule Sponge For Mir-654-3pmentioning

confidence: 99%

See 1 more Smart Citation

Circular RNA circRHOBTB3 acts as a sponge for miR-654-3p inhibiting gastric cancer growth

Deng

Mou

et al. 2020

J Exp Clin Cancer Res

Self Cite

232

167

View full text Add to dashboard Cite

Background: Circular RNAs (circRNAs) have recently emerged as a new family of noncoding RNAs that are involved in the causation and progression of various cancers. However, the roles of circRNAs in the tumorigenesis of gastric cancer (GC) are still largely unknown. Methods: The expression profiles of circRNAs in GC were identified in open GEO database and were evaluated at the mRNA level in clinical GC samples compared with paired non-tumorous tissues. Kaplan-Meier survival curve was used to analyze the correlation of circRNA and patients' prognosis. Subsequently, the circular structures of candidate circRNAs were validated by Sanger sequencing, divergent primer PCR, and RNase R treatments. Gain-and loss-of-function analyses were performed to evaluate the functional significance of it in GC initiation and progression. Dual-luciferase reporter and RNA pull-down assays were used to identify the microRNA (miRNA) sponge mechanism of circRNAs.Results: The expression of circRHOBTB3 was lower in GC tissues and cell lines. Downregulation of circRHOBTB3 was significantly correlated with poor differentiation and unfavorable prognosis in patients with GC. Overexpression of circRHOBTB3 in GC cells led to decreased proliferation and induced G 1 /S arrest in vitro, accompanied with inhibited xenograft tumor growth in vivo, while the opposite effects were achieved in circRHOBTB3-silenced cells. Furthermore, we demonstrated that circRHOBTB3 acts as a sponge for miR-654-3p and verified that p21 is a novel target of miR-654-3p.Conclusion: Taken together, this study revealed that circRHOBTB3 might function as competing endogenous RNA (ceRNA) for miR-654-3p, which could contribute to growth inhibition of GC through activating p21 signaling pathway. Our data suggested that circRHOBTB3 would serve as a novel promising diagnosis marker and therapeutic target for GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Circrhobtb3 Acted As a Molecule Sponge For Mir-654-3pmentioning

confidence: 99%

Circular RNA circRHOBTB3 acts as a sponge for miR-654-3p inhibiting gastric cancer growth

Deng

Mou

et al. 2020

J Exp Clin Cancer Res

Self Cite

232

167

View full text Add to dashboard Cite

show abstract

“…The S100A4‐MYH9 axis could promote migration and invasion through inducing transforming growth factor‐β‐mediated epithelial‐mesenchymal transition in gastric cancer 35 . In addition, MYH9 was downregulated by miR‐124, miR‐647, or let‐7f to suppress invasion and metastasis in colorectal or gastric cancer 36‐38 . It is well known that the Wnt/β‐catenin signaling can promote metastasis and is associated with poor progression in a variety of cancer types, including NPC 39,40 .…”

Section: Discussionmentioning

confidence: 99%

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Yang

et al. 2020

Cancer Science

View full text Add to dashboard Cite

Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.

show abstract

“…Increasing studies have revealed that the dysregulation of miRNAs is strongly associated with the tumorigenesis and progression of cancers, including GC [16-18]. Additionally, miRNAs have been reported to be used as biomarkers of diagnosis [19] and prognosis [20, 21] in GC.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis

Zhang¹,

Ma²,

Wu³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: MicroRNAs have a significant role in the tumorigenesis and progression of cancers, including gastric cancer (GC). Our study aimed to identify a novel biomarker to predict the prognosis of patients with GC. Methods: The GC microarray dataset, GSE28700, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed miRNAs (DEMs). The downregulation of miR-376a expression was verified in GC cell lines and 82 paired GC tissues by performing RT-qPCR and the correlation between its expression and clinicopathological characteristics was also explored. The target genes of miR-376a were predicted using TargetScan7.1, miRDB, and DIANA website tools. A functional enrichment analysis was performed to explore the biological role of the common target genes. Results: Bioinformatics analysis found that miR-376a was downregulated in GC tissues. Compared with the control group, RT-qPCR results showed that the expression of miR-376a in GC cell lines and tissues were also significantly decreased. The expression of miR-376a was statistically associated with T and N stage. Survival analysis with Kaplan–Meier showed that GC patients in the low expression group had a poorer prognosis than those in the high expression group (median survival of 26.4 and 46.9 months, respectively). Univariate and multivariate analysis demonstrated that low miR-376a expression was an independent prognostic marker for poor survival. Functional enrichment analysis indicated that the common targets genes were involved in cell–cell communication, VEGF and mTOR1-mediated signaling, and epithelial-to-mesenchymal transition (EMT). Conclusion: The results suggest that miR-376a could play an important role in the tumorigenesis and progression of GC and act as a novel therapeutic target and prognostic indicator in patients with GC.

show abstract

MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer

Cited by 75 publications

References 46 publications

Circular RNA circRHOBTB3 acts as a sponge for miR-654-3p inhibiting gastric cancer growth

Circular RNA circRHOBTB3 acts as a sponge for miR-654-3p inhibiting gastric cancer growth

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis

Contact Info

Product

Resources

About