Integrative Omic Profiling Reveals Unique Hypoxia Induced Signatures in Gastric Cancer Associated Myofibroblasts

Although hypoxia is known to contribute to several aspects of tumour progression, relatively little is known about the effects of hypoxia on cancer-associated myofibroblasts (CAMs), or the consequences that conditional changes in CAM function may have on tumour development and metastasis. To investigate this issue in the context of gastric cancer, a comparative multiomic analysis was performed on populations of patient-derived myofibroblasts, cultured under normoxic or hypoxic conditions. Data from this study reveal a novel set of CAM-specific hypoxia-induced changes in gene expression and secreted proteins. Significantly, these signatures are not observed in either patient matched adjacent tissue myofibroblasts (ATMs) or non-cancer associated normal tissue myofibroblasts (NTMs). Functional characterisation of different myofibroblast populations shows that hypoxia-induced changes in gene expression not only enhance the ability of CAMs to induce cancer cell migration, but also confer pro-tumorigenic (CAM-like) properties in NTMs. This study provides the first global mechanistic insight into the molecular changes that contribute to hypoxia-induced pro-tumorigenic changes in gastric stromal myofibroblasts.

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KH-type splicing regulatory protein is a new component of chromatoid body

Reproduction ◽

10.1530/rep-17-0169 ◽

2017 ◽

Vol 154 (6) ◽

pp. 723-733 ◽

Cited By ~ 1

Author(s):

Huijuan Zhang ◽

Guishuan Wang ◽

Lin Liu ◽

Xiaolin Liang ◽

Yu Lin ◽

...

Keyword(s):

Gene Expression ◽

Germ Cell ◽

Knockout Mice ◽

Binding Protein ◽

Regulatory Protein ◽

Somatic Cells ◽

Chromatoid Body ◽

Mechanistic Insight ◽

Insight Into

The chromatoid body (CB) is a specific cloud-like structure in the cytoplasm of haploid spermatids. Recent findings indicate that CB is identified as a male germ cell-specific RNA storage and processing center, but its function has remained elusive for decades. In somatic cells, KH-type splicing regulatory protein (KSRP) is involved in regulating gene expression and maturation of select microRNAs (miRNAs). However, the function of KSRP in spermatogenesis remains unclear. In this study, we showed that KSRP partly localizes in CB, as a component of CB. KSRP interacts with proteins (mouse VASA homolog (MVH), polyadenylate-binding protein 1 (PABP1) and polyadenylate-binding protein 2 (PABP2)), mRNAs (Tnp2 and Odf1) and microRNAs (microRNA-182) in mouse CB. Moreover, KSRP may regulate the integrity of CB via DDX5-miRNA-182 pathway. In addition, we found abnormal expressions of CB component in testes of Ksrp-knockout mice and of patients with hypospermatogenesis. Thus, our results provide mechanistic insight into the role of KSRP in spermatogenesis.

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A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000490168 ◽

2018 ◽

Vol 47 (3) ◽

pp. 1025-1041 ◽

Cited By ~ 15

Author(s):

Pengcheng Wang ◽

Jing Li ◽

Wei Zhao ◽

Chunyang Shang ◽

Xian Jiang ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Regulatory Networks ◽

Functional Enrichment ◽

Microrna Target ◽

Kaplan Meier ◽

Important Regulator ◽

Non Coding Rnas ◽

Gc Gene ◽

Insight Into

Background/Aims: Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in gastric cancer (GC) remains unclear. Methods: We reannotated the GC gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global GC triple network. A further clustering and random walk with restart analyses was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine expression of lncRNA RP11-363E7.4. Kaplan-Meier analyses was performed to evaluate the prognostic value of lncRNA RP11-363E7.4. Results: We constructed a gastric cancer lncRNA-miRNA-mRNA network (GCLMN) including six lncRNAs, 332 mRNAs, and 3,707 edges. For the shared lncRNA RP11-363E7.4, the interacting gene and microRNA functional enrichment studies implied that lncRNA RP11-363E7.4 might function as a new regulator in GC. The expression of lncRNA RP11-363E7.4 was downregulated compared with that of paracarcinoma tissues in five GC samples. High expression of lncRNA RP11-363E7.4 was found to be correlated to better overall survival (OS) for GC patients. Conclusions: This study focused on GC lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA RP11-363E7.4 was a new GC risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of GC.

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