MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation.

Abstract

The retinoblastoma is the most common intraocular malignant tumor in infants and children; it is one of the deadliest forms of cancer due to its limited sensitivity to chemotherapy and radiotherapy. In several cancers, chemoresistance is associated with autophagy induction. Non-coding RNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs) have been reported to regulate physiological activities of the cells, including proliferation, apoptosis, migration, as well as autophagy. MALAT1, a well-established lncRNA acts as an oncogene, promotes cancer proliferation, and metastasis via the stimulation of autophagy. In addition to MALAT1, miR-124, a known tumor suppressor, has also been reported to regulate cell apoptosis and autophagy in dopaminergic neurons. In the present study, we investigated the roles of MALAT1 and miR-124 in the regulation of retinoblastoma cell autophagy through evaluating the changes of autophagy-related proteins. Through direct targeting miR-124, MALAT1 promotes retinoblastoma cell autophagy. Further, we investigated whether Syntaxin 17 (STX17), a Soluble NSF Attachment Protein receptor (SNARE) of the autophagosome, is involved in MALAT1/miR-124 regulation of retinoblastoma cell autophagy, and the underlying mechanism. Taken together, we provided novel experimental and theoretical basis for regulation of retinoblastoma cell autophagy, and potential direction of dealing with autophagy-induced chemoresistance of retinoblastoma, which need further in-depth study.