PMID- 29864621 OWN - NLM STAT- MEDLINE DCOM- 20181106 LR - 20211204 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 105 DP - 2018 Sep TI - Downregulation of circular RNA hsa_circ_0001649 indicates poor prognosis for retinoblastoma and regulates cell proliferation and apoptosis via AKT/mTOR signaling pathway. PG - 326-333 LID - S0753-3322(18)32716-1 [pii] LID - 10.1016/j.biopha.2018.05.141 [doi] AB - Retinoblastoma (RB) is the most common intraocular malignancy in infants and children with high mortality rate in developing countries. Emerging evidence demonstrated that abnormally expressed circular RNAs (circRNAs) are involved in tumorigenesis and progression in several malignancies. However, their clinical values, biological functions and mechanisms in RB has not been reported before. Recently, hsa_circ_0001649 was found to play imperative roles in cholangiocarcinoma, gastric cancer, and hepatocellular carcinoma. In the current study, qRT-PCR was performed to detect the expression of hsa_circ_0001649 in RB samples and cells. The correlations between hsa_circ_0001649 expression and clinicopathologic characteristics were further analyzed. In addition, we up-regulated hsa_circ_0001649 in Y79 cells and knocked down hsa_circ_0001649 in WERI-Rb1 cells to explore its effect on cell proliferation and apoptosis. The animal study was performed to confirm the in vitro results. Furthermore, AKT/mTOR signaling pathway was detected to clarify the molecular mechanisms of hsa_circ_0001649 exerts in RB cell growth. The results indicated that hsa_circ_0001649 was decreased in RB tissues and cells, and this downregulation was associated with larger tumor size and advanced intraocular international retinoblastoma classify (IIRC) stage in RB patients. Additionally, hsa_circ_0001649 could act as an independent prognostic predictor for overall survival in patients with RB. Moreover, hsa_circ_0001649 inhibits cell growth and promotes cell apoptosis in RB cells. AKT/mTOR signaling pathway is involved in the cell growth alteration affected by hsa_circ_0001649. Overall, hsa_circ_0001649 might be a potentially useful prognostic biomarker and therapeutic target for RB. CI - Copyright (c) 2018. Published by Elsevier Masson SAS. FAU - Xing, Lichen AU - Xing L AD - Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China. FAU - Zhang, Leiming AU - Zhang L AD - Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China. FAU - Feng, Yali AU - Feng Y AD - Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China. FAU - Cui, Zhe AU - Cui Z AD - Department of Ophthalmology, Third Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China. FAU - Ding, Lin AU - Ding L AD - Department of Clinical Skills Experimental Teaching Center, Qiqihar Medical University, Heilongjiang Province, 161000, China. Electronic address: dlineye@126.com. LA - eng PT - Journal Article DEP - 20180601 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (RNA, Circular) RN - 63231-63-0 (RNA) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis/*genetics MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Child, Preschool MH - Down-Regulation/*genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Infant MH - Male MH - Mice, Nude MH - Multivariate Analysis MH - Neoplasm Invasiveness MH - Phenotype MH - Prognosis MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA/*genetics MH - RNA, Circular MH - Retinoblastoma/*genetics/*pathology/surgery MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - AKT/mTOR pathway OT - Circular RNA OT - Prognosis OT - Retinoblastoma OT - hsa_circ_0001649 EDAT- 2018/06/05 06:00 MHDA- 2018/11/07 06:00 CRDT- 2018/06/05 06:00 PHST- 2018/04/23 00:00 [received] PHST- 2018/05/26 00:00 [revised] PHST- 2018/05/28 00:00 [accepted] PHST- 2018/06/05 06:00 [pubmed] PHST- 2018/11/07 06:00 [medline] PHST- 2018/06/05 06:00 [entrez] AID - S0753-3322(18)32716-1 [pii] AID - 10.1016/j.biopha.2018.05.141 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Sep;105:326-333. doi: 10.1016/j.biopha.2018.05.141. Epub 2018 Jun 1.