MicroRNA-124 facilitates lens epithelial cell apoptosis by inhibiting SPRY2 and MMP-2

Abstract

Age-related cataract (ARC) is the primary cause of blindness worldwide. Abnormal expression of microRNAs (miRNAs/miRs) has been reported to be associated with multiple diseases, including ARC. However, the potential role of miR-124 in ARC remains unclear. The present study used the human lens epithelial cell line, SRA01/04, to investigate the potential role of miR-124 in ARC. Reverse transcription-quantitative PCR analysis was performed to detect the expression levels of miR-124, protein sprouty homolog 2 (SPRY2) and matrix metalloproteinase-2 (MMP-2) in ARC tissues, while western blotting was performed to detect the protein levels of SPRY2 and MMP-2. Cell viability and apoptosis of SRA01/04 cells were assessed via Cell Counting Kit-8 and TUNEL assays, respectively. The interaction between miR-124 and SPRY2 or MMP-2 was confirmed via the dual-luciferase reporter and RNA immunoprecipitation assays. The results of the present study demonstrated that miR-124 expression was significantly upregulated in ARC tissues, and knockdown of miR-124 increased SRA01/04 cell viability and suppressed apoptosis. In addition, SPRY2 and MMP-2 expression was decreased in ARC tissues, and were demonstrated to directly bind to miR-124. Overexpression of SPRY2 or MMP-2 increased SRA01/04 cell viability and repressed apoptosis, the effects of which were reversed following overexpression of miR-124. Taken together, these results suggested that miR-124 facilitates lens epithelial cell apoptosis by modulating SPRY2 or MMP-2 expression, providing a novel treatment approach for ARC.

In Vivo miRNA Decoy Screen Reveals miR-124a as a Suppressor of Melanoma Metastasis

“…To validate miR-124a’s potential function as a metastasis suppressor, we transduced 113/6-4L melanoma cells with lentiviral vectors carrying mCherry-luciferase and a GFP-tagged single decoy against miR-124a (Dc-124a) or a scrambled decoy control (Dc-Scr). We confirmed that the miR-124a decoy efficiently inhibited miR-124, as miR-124a levels were reduced ( Figure 2A ), an indicator of decoy activity ( 33 ), and established targets of miR-124a EZH2 ( 34 ), MAPK14 ( 35 ), and SPRY2 ( 36 ) were significantly upregulated ( Figure 2B ). Nude mice were inoculated with Dc-124a- or Dc-Scr-transduced melanoma cells in the left heart ventricle and monitored by luminescence imaging throughout the experiment ( Figure 2C ).…”

LINC00452 overexpression reverses oxLDL-induced injury of human umbilical vein endothelial cells (HUVECs) via regulating miR-194-5p/IGF1R axis

“…LINC00452 overexpression also notably abolished the effect of oxLDL on lipid accumulation (Figure 3B). It has been reported that the changes in MMP are also associated with the promotion of cell apoptosis (28). Therefore, the degree of MMP in HUVECs was determined.…”

Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na 2 Se0 3 -induced Sprague Dawley rat cataract model

“…Microarray analysis revealed several miRNA expression differences in cataract crystalline lens compared with normal lens tissue [14] . A growing body of research now indicates that the miRNA-mRNA axis regulates the activity of lens epithelial cells and is involved in the development of cataracts [13,15,16] , indicating their potential as a new candidate therapeutic target. For example, the upregulation of Let-7b microRNA has been observed in cataracts and promotes cataract progression [12] .…”

“…For example, the upregulation of Let-7b microRNA has been observed in cataracts and promotes cataract progression [12] . Furthermore, miR-221 and miR-124 were also dysregulated in cataracts, suggesting that these miRNAs may play an important role in the pathogenesis of cataracts [13,16] . Therefore, there is an urgent need to identify promising miRNAs for the non-surgical treatment of cataracts due to the vacancy of effective miRNAs for cataracts.…”

“…Current studies have shown that miRNAs are involved in the biological processes of many diseases including tumors, chronic disease, and infectious disease [9,10] , and they can regulate cell proliferation, differentiation, and invasion, apoptosis, and metastasis [11] . In recent years, many researchers have detected the expression of miRNAs in the lens of cataract patients, and a large amount of evidence shows that miRNAs are closely related to the development of cataracts, which regulate protein synthesis by regulating mRNA levels [12,13] . Microarray analysis revealed several miRNA expression differences in cataract crystalline lens compared with normal lens tissue [14] .…”