MiR-25-3p promotes malignant phenotypes of retinoblastoma by regulating PTEN/Akt pathway. 2019

Wencui Wan, and Weiwei Wan, and Yang Long, and Qiuming Li, and Xuemin Jin, and Guangming Wan, and Fengyan Zhang, and Yong Lv, and Guangying Zheng, and Zhigang Li, and Yu Zhu
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou 450052, China.

Aberrant expression of microRNAs plays an important role in the pathogenesis and progression of retinoblastoma. MiR-25, a member of the miR-106b˜25 cluster, has been reported to be abnormally expressed in retinoblastoma, but the exact role of it remains unclear. In our study, we found that miR-25-3p was upregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-25-3p in retinoblastoma cell line WERI-RB-1 increased cell growth, colony formation, anchorage-independent growth, cell migration and invasion in vitro and tumor xenograft growth in vivo. In contrast, inhibited miR-25-3p expression in retinoblastoma cell line Y79 suppressed cell growth, colony formation, anchorage-independent growth, cell migration and invasion. Through luciferase reporter assay, we found that phosphatase and tensin homolog (PTEN) was a direct target of miR-25-3p. This was verified by western blot that miR-25-3p overexpression suppressed PTEN and activated Akt signaling. In addition, miR-25-3p was found to promote epithelial-mesenchymal transition (EMT) of WERI-RB-1 cells through PTEN/Akt pathway. Western blot analysis revealed that miR-25-3p overexpression increased Vimentin and Snail expression, and suppressed E-cadherin expression, but this could be reversed by restoring PTEN. Moreover, LY294002 treatment or restoring PTEN expression abolished the effects of miR-25-3p on cell invasion, colony formation and anchorage-independent growth in vitro and tumor xenograft growth in vivo. Taken together, our results suggested that miR-25-3p promotes malignant transformation of retinoblastoma cells by suppressing PTEN.

UI MeSH Term Description Entries
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012175 Retinoblastoma A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104) Glioblastoma, Retinal,Glioma, Retinal,Neuroblastoma, Retinal,Eye Cancer, Retinoblastoma,Familial Retinoblastoma,Hereditary Retinoblastoma,Sporadic Retinoblastoma,Cancer, Retinoblastoma Eye,Cancers, Retinoblastoma Eye,Eye Cancers, Retinoblastoma,Familial Retinoblastomas,Glioblastomas, Retinal,Gliomas, Retinal,Hereditary Retinoblastomas,Neuroblastomas, Retinal,Retinal Glioblastoma,Retinal Glioblastomas,Retinal Glioma,Retinal Gliomas,Retinal Neuroblastoma,Retinal Neuroblastomas,Retinoblastoma Eye Cancer,Retinoblastoma Eye Cancers,Retinoblastoma, Familial,Retinoblastoma, Hereditary,Retinoblastoma, Sporadic,Retinoblastomas,Retinoblastomas, Familial,Retinoblastomas, Hereditary,Retinoblastomas, Sporadic,Sporadic Retinoblastomas
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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