Posttranscriptional regulation of MMP‐9 by HuR contributes to IL‐1β‐induced pterygium fibroblast migration and invasion

Abstract

Inflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase‐9 (MMP‐9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The influence of interleukin‐1β (IL‐1β) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP‐9 production was determined with qRT‐PCR and gelatin zymography. The interaction between HuR and MMP‐9 was investigated with RNP immunoprecipitation (IP) followed by RT‐PCR and messenger RNA (mRNA) stability analysis. HuR and MMP‐9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL‐1β could increase the expression and nucleus–cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL‐1β on PTF migration and MMP‐9 production. HuR bound to MMP‐9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP‐9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL‐1β on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.

Ribosomal Protein L23 Drives the Metastasis of Hepatocellular Carcinoma via Upregulating MMP9

“…In particular, MMP9, a member of MMP superfamily, has been confirmed to be deeply involved in the metastasis of liver cancer ( 16 – 18 ). Moreover, it has also been reported that RNA binding protein HuR could increase the expression of MMP9 via maintaining MMP9 mRNA stability ( 19 ), indicating a potential underlying association between RBPs and MMP9 expression.…”

HuR Promotes the Progression of Gastric Cancer through Mediating CDC5L Expression

“…Moreover known as the class embryonic death abnormal visual, widely expressed in mammalian cells [ 3 ]. It has been found to affect mRNA translation [ 21 ], cell responses [ 22 ], and inflammatory tumor formation [ 6 ]. In recent years, more studies have found that HuR is associated with the occurrence and prognosis of different carcinoma, glioma [ 8 ], breast cancer [ 9 ], lung cancer [ 10 ], and colorectal cancer [ 11 ].…”

“…Recently, Xue et al reported that microRNA-133b (miR-133b) plays a suppressor role in several human cancers, as well as glioma [8], colorectal cancer [11]. MicroRNAs (miR-NAs) are small noncoding RNAs that bind to mRNAs and regulate gene expression at the posttranscriptional level [5][6][7]. There are a lot of evidence revealing that miRNAs' expression is maladjusted in many cancers, but more studies are needed to confirm how it affects tumorigenesis and metastasis.…”

“…The first three members are mainly expressed in neural tissues and reproductive organs and related to neural development. HuR can be connected with multiple regulatory factors such as Von Hippel Lindau tumor suppressor (VHL), cyclooxygenase 2 (cox-2) [ 5 ], cyclin A, and matrix metallopeptidase-9 (MMP-9) [ 6 ] and participate in various cell responses and inflammatory tumor formation. In recent years, increasing studies have found that HuR is associated with the occurrence, invasion, metastasis, and prognosis of oesophageal squamous cell carcinoma [ 7 ], glioma [ 8 ], breast cancer [ 9 ], lung cancer [ 10 ], and colorectal cancer [ 11 ].…”

Ribosomal protein L23 drives the metastasis of hepatocellular carcinoma via upregulating MMP9

“…However, molecular mechanisms of MMP9 upregulation in HCC are largely unknown. It has reported that the expression of MMP9 could be upregulated by RNA binding protein HuR via stabilizing of MMP9 mRNA 23 , indicating that RBPs may involve in MMP9 regulation.…”