PMID- 31028199 OWN - NLM STAT- MEDLINE DCOM- 20190820 LR - 20211204 IS - 1791-7549 (Electronic) IS - 0258-851X (Print) IS - 0258-851X (Linking) VI - 33 IP - 3 DP - 2019 May-Jun TI - CCL21 Induces mTOR-dependent MALAT1 Expression, Leading to Cell Migration in Cutaneous T-Cell Lymphoma. PG - 793-800 LID - 10.21873/invivo.11541 [doi] AB - BACKGROUND: Mycosis fungoides (MF) is indolent, but may disseminate to leukemia. We reported that C-C motif chemokine ligand 21 (CCL21) is associated with MF invasion and progression. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA, is associated with several cancer types, however, how it interacts with CCL21 to regulate MF progression, remains unclear. MATERIALS AND METHODS: Expression of long noncoding RNAs MALAT1, antisense noncoding RNA in the INK4 locus (ANRIL), Hox antisense intergenic RNA (HOTAIR), highly up-regulated in liver cancer RNA (HULC), and leukemia-associated non-coding insulin-like growth factor 1 receptor activator RNA 1 (LUNAR1) in tissues from MF was studied using polymerase chain reaction and RNA interference in MF cell line MyLa were used to address this question. RESULTS: Expression of MALAT1 was selectively increased in MF tissues. C-C Chemokine receptor type 7 (CCR7) expression was found to be increased in MyLa cells. CCL21 was found not only to mediate migration, but also to enhance MALAT1 and mammalian target of rapamycin (mTOR) activation in MyLa cells. Knockdown of MALAT1 abrogated CCL21-mediated migration, but not mTOR activation. In contrast, mTOR inhibition reduced CCL21-mediated migration and MALAT1 expression. CONCLUSION: CCL21 induced mTOR activation in MyLa cells, followed by expression of MALAT1, causing cell migration. MALAT1 and mTOR are potential therapeutic targets for MF. CI - Copyright(c) 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Hong, Chien-Hui AU - Hong CH AD - Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. AD - Department of Dermatology, National Yang-Ming University College of Medicine, Taipei, Taiwan, R.O.C. FAU - Lin, Shang-Hung AU - Lin SH AD - Department of Dermatology, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C. FAU - Lee, Chih-Hung AU - Lee CH AD - Department of Dermatology, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C. dermlee@gmail.com. LA - eng PT - Journal Article PL - Greece TA - In Vivo JT - In vivo (Athens, Greece) JID - 8806809 RN - 0 (CCL21 protein, human) RN - 0 (Chemokine CCL21) RN - 0 (MALAT1 long non-coding RNA, human) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Small Interfering) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) MH - Biopsy MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Chemokine CCL21/*metabolism MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Lymphoma, T-Cell, Cutaneous/*genetics/*metabolism/pathology MH - Phosphorylation MH - RNA, Long Noncoding/*genetics MH - RNA, Small Interfering/genetics MH - TOR Serine-Threonine Kinases/*metabolism PMC - PMC6559909 OTO - NOTNLM OT - MALAT1 OT - Mycosis fungoides OT - lncRNA OT - mTOR OT - migration COIS- The Authors declare that they have no competing interests in regard to this study. EDAT- 2019/04/28 06:00 MHDA- 2019/08/21 06:00 PMCR- 2019/05/03 CRDT- 2019/04/28 06:00 PHST- 2019/01/04 00:00 [received] PHST- 2019/01/28 00:00 [revised] PHST- 2019/01/30 00:00 [accepted] PHST- 2019/04/28 06:00 [entrez] PHST- 2019/04/28 06:00 [pubmed] PHST- 2019/08/21 06:00 [medline] PHST- 2019/05/03 00:00 [pmc-release] AID - 33/3/793 [pii] AID - 10.21873/invivo.11541 [doi] PST - ppublish SO - In Vivo. 2019 May-Jun;33(3):793-800. doi: 10.21873/invivo.11541.