title: RP5-833A20.1/miR-382-5p/NFIA-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis and inflammatory reaction.
abstract: OBJECTIVE
  Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear.
  
  
  RESULTS
  Using microarray analysis, we found that long noncoding RNA RP5-833A20.1 expression was upregulated, whereas nuclear factor IA (NFIA) expression was downregulated in human acute monocytic leukemia macrophage-derived foam cells. Moreover, we showed that long noncoding RNA RP5-833A20.1 may decreases NFIA expression by inducing hsa-miR-382-5p expression in vitro. We found that the RP5-833A20.1/hsa-miR-382-5p/NFIA pathway is essential to the regulation of cholesterol homeostasis and inflammatory responses in human acute monocytic leukemia macrophages. Lentivirus-mediated NFIA overexpression increased high-density lipoprotein cholesterol circulation, reduced low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol circulation, decreased circulation of inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein, enhanced reverse cholesterol transport, and promoted regression of atherosclerosis in apolipoprotein E-deficient mice.
  
  
  CONCLUSIONS
  Our findings indicated that the RP5-833A20.1/miR-382-5p/NFIA pathway was essential to the regulation of cholesterol homeostasis and inflammatory reactions and suggested that NFIA may represent a therapeutic target to ameliorate cardiovascular disease.
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Huang
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Shao-Guo
authors.initials: SG
authors.lastname: Wu
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Chen
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Ya-Rong
authors.initials: YR
authors.lastname: Hu
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jun-Yao
authors.initials: JY
authors.lastname: Yang
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Wang
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Ji-Juan
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Sha
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. nfyywangqian@163.com nfyyzl@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: From the Laboratory Medicine Center (Y.-W.H., J.-Y.Z., S.-F.L., J.-L.H., Y.-R.Q., S.-G.W., Z.-P.C., Y.-R.H., J.-Y.Y., Y.-C.W., J.-J.G., Y.-H.S., L.Z., Q.W.) and Department of Anesthesiology (X.M.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. nfyywangqian@163.com nfyyzl@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D018938:Caco-2 Cells; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood; D016086:Lentivirus / Q000235:genetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: C544065:AGTR1 protein, human; D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C555413:MIRN382 microRNA, human; D035683:MicroRNAs; D051839:NFI Transcription Factors; C497592:NFIA protein, human; C497646:Nfia protein, mouse; D062085:RNA, Long Noncoding; C000595375:RP5-833A20.1 long non-coding RNA, mouse; D044140:Receptor, Angiotensin, Type 1; C099252:oxidized low density lipoprotein; D002784:Cholesterol
keywords: NFIA protein, human; RNA, long noncoding; atherosclerosis