PMID- 30994959 OWN - NLM STAT- MEDLINE DCOM- 20200831 LR - 20211204 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 120 IP - 8 DP - 2019 Aug TI - Silencing of microRNA-27a facilitates autophagy and apoptosis of melanoma cells through the activation of the SYK-dependent mTOR signaling pathway. PG - 13262-13274 LID - 10.1002/jcb.28600 [doi] AB - Melanoma is considered as an aggressive neoplastic transformation and featured with high metastatic potential. Although some studies have provided targets for novel therapeutic interventions, clinical development of targeted drugs for melanoma still remains obscure. Therefore, this study aims to identify the role of microRNA-27a (miR-27a) in autophagy and apoptosis of melanoma cells in regulating spleen tyrosine kinase (SYK)-mediated the mammalian target of rapamycin (mTOR) signaling pathway. A microarray-based analysis was made to screen differentially expressed genes and predict target miRNA. Melanoma specimens were collected with pigmented nevus as a control. Melanoma cell line Mel-RM was treated with miR-27a inhibitor or pcDNA-SYK to prove their effects on autophagy and apoptosis of melanoma cells. The volume change and tumor mass of nude mice in each group were detected by the tumorigenesis assay. Microarray-based analysis results showed that SYK was lowly expressed in melanoma cells and may be regulated by miR-27a. Besides, miR-27a expression was increased whereas SYK expression was decreased in melanoma tissues. Meanwhile, miR-27a was positively correlated with tumor stage and lymph node metastasis of melanoma tissues. Furthermore, miR-27a targeted SYK and silencing of miR-27a or overexpression of SYK cells promoted autophagy and apoptosis of melanoma cells and reduced their tumorigenic ability in vivo. In conclusion, this study proves that silencing of miR-27a facilitates autophagy and apoptosis of melanoma cells by upregulating SYK expression and activating the mTOR signaling pathway. The finding offers new ideas for the clinical development of melanoma. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Tang, Hua AU - Tang H AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Xu, Xiaopeng AU - Xu X AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Xiao, Weirong AU - Xiao W AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Liao, Yangying AU - Liao Y AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Xiao, Xiao AU - Xiao X AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Li, Lan AU - Li L AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Li, Ke AU - Li K AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Jia, Xiaomin AU - Jia X AD - Department of Pathology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. FAU - Feng, Hao AU - Feng H AUID- ORCID: 0000-0001-9850-0422 AD - Department of Dermatology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190417 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (MIRN27 microRNA, human) RN - 0 (MicroRNAs) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis/genetics/physiology MH - Autophagy/genetics/*physiology MH - Cell Line, Tumor MH - Female MH - Humans MH - Immunohistochemistry MH - Melanoma/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/*metabolism MH - Signal Transduction/genetics/*physiology MH - TOR Serine-Threonine Kinases/genetics/*metabolism OTO - NOTNLM OT - apoptosis OT - autophagy OT - mammalian target of rapamycin (mTOR) signaling pathway OT - melanoma OT - microRNA-27a (miR-27a) OT - spleen tyrosine kinase (SYK) EDAT- 2019/04/18 06:00 MHDA- 2020/09/01 06:00 CRDT- 2019/04/18 06:00 PHST- 2018/12/28 00:00 [received] PHST- 2019/02/11 00:00 [accepted] PHST- 2019/04/18 06:00 [pubmed] PHST- 2020/09/01 06:00 [medline] PHST- 2019/04/18 06:00 [entrez] AID - 10.1002/jcb.28600 [doi] PST - ppublish SO - J Cell Biochem. 2019 Aug;120(8):13262-13274. doi: 10.1002/jcb.28600. Epub 2019 Apr 17.