Suppression of microRNA-125a-5p upregulates the TAZ-EGFR signaling pathway and promotes retinoblastoma proliferation.
Retinoblastoma is the most common intraocular malignancy that occurs during childhood; however, the mechanism underlying retinoblastoma proliferation and progression remains unclear. MicroRNAs (miRNAs) play an important role in the regulation of a myriad of biological processes in various types of cancer. In this study, we performed microarray analysis followed by qRT-PCR using four classes of retinoblastoma tissues with increasing cTNM classification stages to identify crucial miRNAs whose expression was correlated with retinoblastoma progression. miR-125a-5p was downregulated, and its expression levels were inversely correlated with cell proliferation in retinoblastoma compared with adjacent non-tumor retinal tissues. The overexpression of miR-125a-5p significantly suppressed cell proliferation and tumor formation in retinoblastoma. We further identified the transcriptional co-activator with PDZ binding motif (TAZ) as a direct target of miR-125a-5p. Importantly, TAZ levels were inversely correlated with miRNA-125a-5p expression, and TAZ promoted retinoblastoma cell proliferation. Moreover, the overexpression of miR-125a-5p led to a decrease in TAZ expression and downstream EGFR signaling pathway activation both in vitro and vivo. Finally, TAZ overexpression in retinoblastoma cells overexpressing miR-125a-5p restored retinoblastoma cell proliferation and EGFR pathway activation. Taken together, our data demonstrated that miR-125a-5p functions as an important tumor suppressor that suppresses the EGFR pathway by targeting TAZ to inhibit tumor progression in retinoblastoma. Thus, the miR-125a-5p/TAZ/EGFR axis may be a potential therapeutic target for retinoblastoma.
Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China.
Yiting
Y
Zhang
Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China; Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China.
Chunyan
C
Xue
Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China.
Xiaomin
X
Zhu
Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China.
Xinyue
X
Zhu
Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China.
Hongyu
H
Xian
Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China; Department of Ophthalmology, Jinling Hospital, Nanjing 210002, China. Electronic address: huangzhenping19633@163.com.
Zhenping
Z
Huang
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics*
D019927:Cyclin E; D047908:Intracellular Signaling Peptides and Proteins; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D066246:ErbB Receptors; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
Proliferation; Retinoblastoma; TAZ; miR-125a-5p; microRNAs