Abstract
Retinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.
Highlights
Retinoblastoma is the most common malignancy in children’s eyes (Stark 2016)
FEZF1-AS1 silencing inhibited cell viability (Fig. 1e). These data indicated that FEZF1-AS1 was abnormal expressed in retinoblastoma patients and cells, and FEZF1-AS1 affected retinoblastoma cell viability
The interaction between FEZF1-AS1 and miR-363-3p was further tested using RNA Immunoprecipitation (RIP) assay, and the results revealed that both FEZF1-AS1 and miR-363-3p were enriched in input or Ago2containg immunoprecipitates compared with that in IgG immunoprecipitates (Fig. 3c)
Summary
Retinoblastoma is the most common malignancy in children’s eyes (Stark 2016). Retinoblastoma is accompanied by multiple lesions and exhibits intracranial and systemic metastasis when the tumor grows and breaks through the eyeball (Garsed et al 2018). It has reported that lncRNAs show important roles in the progression of human tumors (Tsai et al 2011; Tang et al 2013), including retinoblastoma (Wang et al 2018; Yang and Peng 2018). Accumulating evidences have shown that mRNAs played an important role in development of retinoblastoma (Reis et al 2012). It is interesting to investigate the role of miR-363-3p in development of retinoblastoma. The expression of FEZF1-AS1 was measured in retinoblastoma tissues and cells. The role of FEZF1-AS1 in progression of retinoblastoma was explored. We further investigated whether FEZF1-AS1 functions in progression of retinoblastoma through miR-363-3p. The study suggests that FEZF1-AS1 may provide a candidate target for retinoblastoma treatment
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