miR-133b Regulation of Connective Tissue Growth Factor

Abstract

miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response. (Am J Pathol 2016 http://dx

CTGF Contributes to the Development of Posterior Capsule Opacification: an in vitro and in vivo study

“…Studies have shown that CTGF can activate multiple signalling pathways, including ERK, p38, JNK, ROS, ASK1 and NF-κB, and promote the migration and proliferation of human Tenon's capsule fibroblasts, hepatic stellate cells (HSCs), hepatoma carcinoma cells, cardiomyocytes and glioma cells 17 - 22 . Our former research findings showed that CTGF is under the regulation of the TGF-β/Smad signalling pathway.…”

CTGF/VEGFA-activated Fibroblasts Promote Tumor Migration Through Micro-environmental Modulation

“…To our knowledge, CTGF and VEGFA have not been previously implicated in fibroblast activation. Although CTGF level is regulated via miRNA mechanisms in the contexts of liver pathology (22), diabetic nephropathy (23), and hyperplastic scar formation (24), these studies focused exclusively on autocrine effects, whereas the paracrine effect of tumor-secreted CTGF on other cell types in the tumor vicinity has not been studied. Similarly, VEGFA has a well-established role in tumor vascularization, but its function has not been linked to fibroblast activation, even though the duration of fibroblast activation appears to coincide well with the induction of new blood vessels prior to metastatic spread (17).…”

miR-133b, a particular member of myomiRs, coming into playing its unique pathological role in human cancer

“…Two members of the BCL-2 family of pro-survival molecules (MCL-1 and BCL2L2 (BCLw)) as predicted targets of miR-133b have been identified in lung cancer, osteosarcoma, bladder cancer and gastric cancer (Mcl-1 and Bcl-xL), in which over-expression of miR-133b can induce apoptosis though theses apoptosis regulator in tumor cells [ 27 – 30 ]. Yet expect all the apoptotic pathways, miR-133b can regulate genes closely related to proliferation, such as fibroblast growth factor receptor 1 (FGFR1), and Sp1 and its downstream proteins Cyclin D1 in gastric cancer [ 31 , 32 ], TATA-box binding protein like 1(TBPL1) in colorectal cancer [ 33 ], the human ether-a-go-go-related gene potassium channel (hERG, Kv11.1, KCNH2) in glioma [ 34 ]and connective tissue growth factor(CTGF) in hepatocellular carcinoma (HCC) [ 35 ].…”

“…(Figure 3B, 3C ), Table 1 . Fascin actin-bundling protein 1(FSCN1), which plays a critical role in cell migration, motility, adhesion and cellular interactionsin, in esophageal squamous cell carcinoma (ESCC) [ 61 ], gastrointestinal stromal tumor(GIST) [ 62 ] and gastric cancer [ 63 ], C-X-C motif chemokine receptor 4(CXCR4) and in colorectal cancer [ 64 ], IGF1R, MET, phospho-Akt and FAK in osteosarcoma [ 28 ], Gli1 in gastric cancer(GC) [ 65 ], Sp1 and its downstream proteins MMP-9 in GC [ 32 ], CTGF in HCC [ 35 ].…”