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A Review on the Correlation between the Pathology of Alzheimer's Disease and microRNA
Biomed Sci Letters 2021;27:208-215
Published online December 31, 2021;  https://doi.org/10.15616/BSL.2021.27.4.208
© 2021 The Korean Society For Biomedical Laboratory Sciences.

Soo-Jung Kim* and Hyun-Jeong Cho†,**

Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Korea
Correspondence to: *Graduate student, **Professor.
Corresponding author: Hyun-Jeong Cho. Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Korea.
Tel: +82-42-600-8433, Fax: +82-42-600-8408, e-mail: hjcho@konyang.ac.kr
Received October 28, 2021; Revised December 10, 2021; Accepted December 10, 2021.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
The purpose of this study was to explain the pathology of Alzheimer's disease (AD) and to investigate the correlation between AD and microRNA. AD is the most common type of dementia, accounting for about 80% of all types of dementia, causing dysfunction in various daily activities such as memory loss, cognitive impairment, and behavioral impairment. The typical pathology of AD is explained by the accumulation of beta-amyloid peptide plaques and neurofibrillary tangles containing hyperphosphorylated tau protein. On the other hand, microRNA is small non-coding RNA 22~23 nucleotides in length that binds to the 3' untranslated region of messenger RNA to inhibit gene expression. Many reports explain that microRNAs found in circulating biofluids are abundant in the central nervous system, are involved in the pathogenic mechanism of AD, and act as important factors for early diagnosis and therapeutic agents of AD. Therefore, this paper aims to clarify the correlation between AD and microRNA. In this review, the basic mechanism of miRNAs is described, and the regulation of miRNAs in the pathological processes of AD are highlighted. Furthermore, we suggest that miRNA-based system in development of therapeutic and diagnostic agents of AD can be a promising tool.
Keywords : Alzheimer's disease, Beta-amyloid plaques, Neurofibrillary tangles, MicroRNA, Biomarker
1. 꽌濡

移섎ℓ(dementia)뒗 珥덇린뿉 씤吏 쁺뿭쓽 븯濡쒕꽣 떆옉빐꽌 湲곗뼲, 뼵뼱떎뻾, 떆怨듦컙 씤吏 湲곕뒫, 꽦寃 諛 뻾룞쓣 룷븿븯뿬 씪긽깮솢뿉꽌쓽 湲곕낯 솢룞쓣 닔뻾븯뒗 뒫젰쓣 긽떎븯뒗 엫긽 利앺썑援곗씠떎(Weller and Budson, 2018). 븳렪, 븣痢좏븯씠癒몃퀝(Alzheimer's disease, AD) 紐⑤뱺 移섎ℓ쓽 理쒕 80%瑜 李⑥븯뒗 媛옣 쓷븳 쑀삎쓽 移섎ℓ씠떎. 씠 吏덊솚 씪諛섏쟻쑝濡 뇤쓽 궡痢 痢〓몢뿽 諛 떊뵾吏 援ъ“뿉 踰좏-븘諛濡쒖씠뱶(beta-amyloid peptide, Aβ)쓽 異뺤쟻怨 떊寃쎌꽟쑀 떎諛(neurofibrillary tangle, NFT)쓽 利앷瑜 듅吏뺤쑝濡 꽌꽌엳 吏꾪뻾릺뒗 떊寃쏀눜뻾꽦 吏덊솚씠떎(Weller and Budson, 2018; Breijyeh and Karaman, 2020). 씪諛섏쟻쑝濡 吏덈퀝쓽 利앹긽 媛踰쇱슫 湲곗뼲젰 옣븷濡 떆옉븯吏留, 씤吏 옣븷, 湲곕뒫 옣븷濡 諛쒖쟾븳떎. 洹몃윭굹 議곌린吏꾨떒 떆뒪뀥씠 븘吏 媛뽰텛뼱졇 엳吏 븡븘꽌 븣痢좏븯씠癒몃퀝쑝濡 솗吏꾩씠 릺뿀떎硫, 뿬윭 뇤 쁺뿭뿉꽌 떊寃쎌꽭룷 냼떎怨 떊寃쎈퀝由ы븰쟻 蹂묐씠 씠誘 留롮씠 吏꾪뻾릺뿀떎怨 븣젮졇 엳떎(Mantzavinos and Alexiou, 2017). 몴쟻쑝濡 떊寃쎌꽭룷 떆깄뒪쓽 눜뻾 뇤뵾吏(cerebral cortex)怨 빐留(hippocampus)뿉꽌 媛옣 몢뱶윭吏寃 굹굹怨 엳쑝硫, 援ъ“쟻 蹂솕 븿猿 湲곕뒫 긽떎, 궛솕 뒪듃젅뒪 諛 誘명넗肄섎뱶由ъ븘 湲곕뒫 옣븷 愿젴맂 떊寃 뿼利앹쓽 蹂솕瑜 珥덈옒븳떎怨 븣젮졇 엳떎(Ausó et al., 2020).

븳렪, 븣痢좏븯씠癒몃퀝怨쇱쓽 긽愿꽦쓣 꽕紐낇븯怨좎옄 븯뒗 microRNA (miRNA)뒗 빟 22媛쒖쓽 돱겢젅삤씠뱶濡 援ъ꽦릺硫, 떒諛깆쭏 諛쒗쁽쓣 븯뼢 삉뒗 긽뼢 議곗젅븯뒗 옉 鍮꾩븫샇솕 떒씪 媛떏 RNA濡, messenger RNA (mRNA)쓽 以묒슂븳 쟾궗 썑 議곗젅 씤옄씠떎(Wei et al., 2020; Wu et al., 2020). 떒씪 miRNA뒗 닔諛 媛쒖쓽 mRNA瑜 몴쟻쑝濡 븯硫, 湲곕뒫쟻쑝濡 긽샇뿰寃 릺뼱 엳뒗 留롮 쑀쟾옄쓽 諛쒗쁽뿉 쁺뼢쓣 誘몄튇떎(Lu and Rothenberg, 2018). miRNA 諛쒗쁽쓽 蹂솕뒗 蹂묓깭깮由ы븰쟻 蹂솕 愿젴씠 엳뼱 理쒓렐 留롮 吏덈퀝뿉꽌 miRNA 諛쒗쁽쓽 蹂솕뿉 愿븳 뿰援ш 닔뻾릺怨 엳떎. 듅엳 뇤 諛쒕떖, 젙긽쟻씤 뇤 끂솕 怨쇱젙 諛 떎뼇븳 떊寃 옣븷뿉꽌 miRNA쓽 뿭븷뿉 愿븳 留롮 뿰援ш 엳떎(Sheinerman et al., 2017). 理쒓렐 떎뼇븳 떊寃 옣븷 諛 떊寃쏀눜뻾뿉 miRNA媛 옞옱쟻쑝濡 愿뿬븿쓣 떆궗븯硫 以묒텛떊寃쎄퀎넻(central nervous system, CNS)쓽 湲곕뒫 諛 蹂묐━븰뿉꽌 miRNA쓽 以묒슂꽦씠 솗씤릺怨 엳떎(Prendecki and Dorszewska, 2014). 쑀쟾옄 議곗젅 쇅뿉룄 miRNA뒗 꽭룷 媛 떊샇 쟾떖뿉꽌 以묒슂븳 뿭븷쓣 븳떎(Li et al., 2021). 遺遺꾩쓽 miRNA뒗 꽭룷 궡遺뿉꽌 諛쒓껄릺吏留, 쇅遺濡 씠룞븷 닔룄 엳뼱 씠瑜 닚솚븯뒗 miRNA씪怨 몴쁽븳떎. 씠뱾 議곗쭅 넀긽, 꽭룷옄硫몄궗(apoptosis) 諛 愿댁궗(necrosis) 諛섏쓳 떆 삁븸 諛 湲고 泥댁븸쑝濡 諛⑹텧릺硫댁꽌 吏덊솚쓽 긽깭瑜 븣젮二쇰뒗 以묒슂븳 臾쇱쭏씠 맆 닔 엳떎(Manna et al., 2020). 뜑슧씠, miRNA뒗 떊寃쎌꽭룷 遺꾪솕 諛 떆깄뒪 媛냼꽦怨 媛숈 깮由ъ쟻 怨쇱젙쓣 議곗젅븷 닔 엳뒗 떊寃쎄퀎뿉꽌룄 留롮씠 諛쒓껄릺湲 븣臾몄뿉(Gugliandolo et al., 2020), 븣痢좏븯씠癒몃퀝怨 媛숈 떊寃쏀눜뻾꽦 吏덊솚쓽 蹂묐━븰쟻 긽깭瑜 吏꾨떒븯뒗 諛붿씠삤留덉빱濡쒖꽌쓽 뿭븷쓣 븷 닔 엳쓣 寃껋쑝濡 궗猷뚮맂떎. 蹂 끉臾몄뿉꽌뒗 븣痢좏븯씠癒몃퀝쓽 蹂묐━ 쁽긽뿉 빐 꽕紐낇븯怨, 븣痢좏븯씠癒몃퀝怨 miRNA쓽 긽愿꽦쓣 젣떆빐 miRNA媛 븣痢좏븯씠癒몃퀝쓽 吏꾨떒 諛 移섎즺瑜 쐞븳 諛붿씠삤留덉빱濡쒖꽌쓽 媛뒫꽦씠 엳쓬쓣 蹂댁뿬二쇨퀬옄 븳떎.

2. 븣痢좏븯씠癒몃퀝쓽 蹂묐━ 쁽긽

븣痢좏븯씠癒몃퀝 솚옄쓽 뇤뒗 룆꽦쓣 쓣뒗 빟 39~43媛 븘誘몃끂궛 湲몄씠쓽 鍮꾩젙긽 떒諛깆쭏怨 援щ━, 泥 삉뒗 븘뿰怨 媛숈 湲덉냽 씠삩씠 븿猿 쓳吏묐맂 삎깭쓽 踰좏-븘諛濡쒖씠뱶 뵆씪겕(plaque)쓽 異뺤쟻怨 誘몄꽭냼愿 븞젙솕 떒諛깆쭏씤 슦(tau)媛 鍮꾩젙긽쟻쑝濡 怨쇱씤궛솕릺뼱 룆꽦 슦 떊寃쎌꽟쑀 떎諛쒖쓣 삎꽦븯뒗 듅吏뺤쓣 媛뽯뒗떎(Athanasopoulos et al., 2016; Serrano-Pozo et al., 2021; Zetterberg and Burnham, 2019; Congdon and Sigurdsson, 2018).

븣痢좏븯씠癒몃퀝쓽 떊寃쎈퀝由ы븰쟻 듅吏뺤 떊뵾吏 떆깄뒪쓽 넀긽 諛 깉씫, 떊寃쎌쐞異 諛 떊寃쎌꽭룷 궗硫, 踰좏-븘諛濡쒖씠뱶 뵆씪겕쓽 異뺤쟻怨 怨쇱씤궛솕맂 슦 떒諛깆쭏 쓳吏묒씠 젙긽 떊寃쎌꽭룷쓽 꽭룷 援ъ“瑜 뙆愿댄븯뿬 꽭룷쓽 뿼利앹쓣 쑀諛쒗븯怨 肄쒕┛꽦 湲곕뒫쓣 媛먯냼떆궓떎怨 븣젮졇 엳떎(Eyileten et al., 2021; Zhao et al., 2020).

븣痢좏븯씠癒몃퀝쓽 蹂묐━븰쟻 듅吏뺤 痢〓몢뿽뿉꽌 떆옉빐 뇤뵾吏 쁺뿭쑝濡 띁吏硫, 留먭린뿉뒗 쟾 뇤 쁺뿭뿉 嫄몄퀜 쁺뼢쓣 諛쏅뒗뜲, 몴쟻쑝濡 븣痢좏븯씠癒몃퀝뿉꽌 굹굹뒗 蹂묐━븰쟻 듅吏뺤씤 踰좏-븘諛濡쒖씠뱶 뵆씪겕 슦 怨쇱씤궛솕濡 씤빐 깮湲 떊寃쎌꽟쑀 떎諛쒖쓣 젣떆븯怨, miRNA 븣痢좏븯씠癒몃퀝怨쇱쓽 긽愿愿怨꾨 굹궡뒗 뿰援ы쁽솴쓣 꽕紐낇븯怨좎옄 븳떎.

2.1 踰좏-븘諛濡쒖씠뱶 뵆씪겕(beta-amyloid plaques)

븘諛濡쒖씠뱶 쟾援ъ껜 떒諛깆쭏(amyloid precursor protein, APP) 21踰 뿼깋泥댁쓽 APP 쑀쟾옄뿉 쓽빐 븫샇솕릺硫(Kent et al., 2020), 遺꾨퉬 諛 꽭룷 궡 씠엯 寃쎈줈瑜 넻빐 쟾떖릺뒗 쑀삎 I 留 愿넻 떒諛깆쭏(type I transmembrane protein)씠硫(Wilkins and Swerdlow, 2017), 씠 떒諛깆쭏 α-, β-, γ-遺꾨퉬 슚냼(secretase)씪怨 븯뒗 꽭 媛吏 遺꾨퉬슚냼뿉 쓽빐 泥섎━맂떎. α-遺꾨퉬 슚냼뒗 議곗젅 湲곕뒫씠 엳뒗 젅렪씤 APP (CT83)쓽 C-留먮떒 젅렪(C-terminal fragment)뿉꽌 APP瑜 83媛 븘誘몃끂궛 媛슜꽦 렔씠뱶濡 쟾솚븳떎. β-遺꾨퉬 슚냼뒗 99媛 븘誘몃끂궛(CT99) 湲몄씠쓽 N-留먮떒 젅렪(N-terminal fragment)쓣 젅떒븯硫 꽭룷留됱뿉 寃고빀븳 긽깭濡 궓븘 엳떎. 삉븳 γ-遺꾨퉬 슚냼뒗 CT83 諛 CT99瑜 Aβ40 諛 Aβ42 삎깭쓽 Aβ 렔씠뱶濡 궗떆궓떎(Rabbito et al., 2020). 씠젃벏씠 踰좏-븘諛濡쒖씠뱶뒗 떎뼇븳 議곗쭅, 듅엳 CNS뿉꽌 諛쒗쁽릺뒗 APP쓽 N-留먮떒뿉꽌 β-遺꾨퉬 슚냼 諛 C-留먮떒뿉꽌 γ-遺꾨퉬 슚냼뿉 쓽븳 슚냼쟻 젅떒 썑뿉 깮꽦맂떎. 理쒓렐뿉뒗 젅떒 슚쑉쓣 理쒕솕븯湲 쐞빐 遺꾨퉬슚냼媛 multi-protease complex瑜 삎꽦븯뒗 寃껋쑝濡 諛앺議뚮떎(Kent et al., 2020; Cheignon et al., 2018; Nasaruddin et al., 2020). 踰좏-븘諛濡쒖씠뱶 떒웾泥대뒗 떊寃쎌꽭룷 떊寃쎄탳꽭룷(glia)뿉꽌 鍮좊Ⅴ寃 踰좏-븘諛濡쒖씠뱶 뵆씪겕濡 쓳吏묒씠 릺硫댁꽌 룆꽦쓣 굹궡寃 릺뒗뜲(Nasaruddin et al., 2020; Kim et al., 2020), 씠寃껋 씠誘 留롮 뿰援ъ뿉꽌 븣痢좏븯씠癒몃퀝怨 愿젴씠 엳쓬씠 諛앺議뚭린 븣臾몄뿉 븣痢좏븯씠癒몃퀝 뿰援ъ뿉꽌 빑떖쟻씤 寃(Target)씠 릺怨 엳떎(Rasgado et al., 2020).

踰좏-븘諛濡쒖씠뱶 異뺤쟻 誘명넗肄섎뱶由ъ븘 궛솕솚썝 洹좏삎뿉 쁺뼢쓣 誘몄퀜 궛솕 뒪듃젅뒪瑜 利앷떆궓떎怨 븣젮졇 엳쑝굹(Fracassi et al., 2021), 씠윭븳 궛솕 뒪듃젅뒪媛 踰좏-븘諛濡쒖씠뱶 깮꽦쓣 쑀諛쒗븯뒗 湲곗쟾 븘吏 紐낇솗븯寃 諛앺吏吏 븡븯떎. 洹몃윭굹 씪遺 뿰援ъ뿉꽌뒗 궛솕 뒪듃젅뒪媛 p38 mitogen 솢꽦솕 떒諛깆쭏 궎굹븘젣 떊샇 쟾떖 寃쎈줈瑜 넻빐 뇤뿉 踰좏-븘諛濡쒖씠뱶 깮꽦 諛 異뺤쟻뿉 湲곗뿬븿쑝濡쒖뜥 븣痢좏븯씠癒몃퀝쓣 쑀諛쒗븳떎怨 젣떆븯怨 엳떎(Wang et al., 2020).

2.2 떊寃쎌꽟쑀 떎諛(neurofibrillary tangle)

떊寃쎌꽟쑀 떎諛쒖쓽 二쇱슂 援ъ꽦슂냼뒗 二쇰줈 떊寃쎌꽭룷뿉꽌 諛쒗쁽릺뒗 슦 떒諛깆쭏씠떎(Naseri et al., 2019). 以묒텛 諛 留먯큹 떊寃쎄퀎뿉꽌 二쇰줈 諛쒗쁽릺뒗 슦뒗 뿼깋泥 17q21뿉 엳뒗 16媛쒖쓽 뿊넀쓣 룷븿븯뒗 誘몄꽭냼愿 愿젴 떒諛깆쭏濡쒖뜥 슦(microtubule-associated protein tau, MAPT) 쑀쟾옄뿉 쓽빐 븫샇솕맂떎(Pîrşcoveanu et al., 2017). 슦 떒諛깆쭏 N-留먮떒 룄硫붿씤, proline 뭾遺 쁺뿭, 諛섎났 룄硫붿씤 諛 C-留먮떒 룄硫붿씤쑝濡 굹돇怨 二쇰줈 誘몄꽭냼愿쓣 븞젙솕떆궎뒗 湲곕뒫쓣 븯굹, 씠윭븳 슦 떒諛깆쭏쓽 怨쇱씤궛솕뒗 븣痢좏븯씠癒몃퀝쓽 以묒슂븳 蹂묐━ 쁽긽 以 븯굹씠떎(Huang and Mucke, 2012; Goedert, 2018). 삉븳 꽭룷 떊샇 쟾떖, 떆깄뒪 媛냼꽦 諛 寃뚮냸 븞젙꽦 議곗젅뿉룄 以묒슂븳 뿭븷쓣 븳떎(Michalicova et al., 2020). 슦 떒諛깆쭏 glycogen synthase kinase(GSK) 3β cyclin-dependent kinase 5 (Cdk5)쓽 옉슜쓣 넻빐 씤궛솕 릺뒗뜲(Guan et al., 2021), 슦 떒諛깆쭏씠 怨좊룄濡 怨쇱씤궛솕릺硫 援ъ“쟻 蹂솕瑜 寃れ쑝硫 뜑 씠긽 誘몄꽭냼愿뿉 寃고빀븷 닔 뾾寃 맂떎(Hamano et al., 2021). 삉븳, 怨쇱씤궛솕濡 씤빐 슦 떒諛깆쭏怨 誘몄꽭냼愿(tau microtubule, MT)쓽 寃고빀 듅꽦씠 넀떎릺硫 삱由ш퀬癒명솕(oligomerization) 諛 떊寃쎌꽟쑀 떎諛쒕줈 쓳吏묓븯뒗 뙇쓣 씠猷⑤뒗 굹꽑 븘씪硫섑듃(paired helical filaments, PHF)쓽 삎꽦쓣 쑀룄븳떎(Canepa and Fossati, 2021). 寃곕줎쟻쑝濡, 鍮꾩젙긽쟻쑝濡 怨쇱씤궛솕맂 슦 떒諛깆쭏(hyperphosphorylated tau protein) 誘몄꽭냼愿 븞젙꽦쓣 쑀吏븯뒗 湲곕뒫쓣 긽떎븯怨, 寃곌낵쟻쑝濡 誘몄꽭냼愿씠 愿뿬븯뒗 異뺤궘 닔넚 떊샇 쟾떖쓣 뼲젣븯寃 맂떎. 씠뒗 由ъ냼醫 삎꽦쓣 諛⑺빐븯怨 異뺤궘뿉꽌쓽 룆꽦 떒諛깆쭏 쓳吏묒뿉 湲곗뿬븯뿬 븣痢좏븯씠癒몃퀝쓣 씪쑝궎뒗 二쇱슂븳 蹂묐━ 쁽긽쓣 젣怨듯븳떎(Jiang et al., 2019).

3. 븣痢좏븯씠癒몃퀝怨 miRNA쓽 긽愿꽦

뇤뿉꽌 留롮씠 諛쒗쁽릺뒗 寃껋쑝濡 諛앺吏 miRNA뒗 뇤泥숈닔븸(cerebrospinal fluid, CSF), 꽭룷쇅븸(extracellular fluid, ECF), 蹂듬쭑븸(peritoneal fluid), 쓨닔(pleural fluid), 젙븸(seminal fluid), 湲곌吏 遺꾨퉬臾(bronchial secretions), 紐⑥쑀(breast milk), 삁泥(serum), 삁옣(plasma) 諛 湲고 떎뼇븳 泥댁븸뿉꽌룄 諛쒓껄맂떎. 삉븳 mRNA 떖由 깮臾쇳븰쟻 寃泥댁뿉꽌 異⑸텇엳 븞젙쟻쑝濡 議댁옱븳떎(Angelucci et al., 2019). 씠뒗 miRNA媛 뼱뼡 泥댁븸뿉꽌뱺 븞젙쟻쑝濡 議댁옱븯湲 븣臾몄뿉 吏덈퀝쓽 諛붿씠삤留덉빱濡쒖뜥 以묒슂븳 寃잛씠 맆 닔 엳쓬쓣 쓽誘명븳떎(Amakiri et al., 2019; Van Giau and An, 2016; Wang et al., 2019). miRNA뒗 듅엳 CNS뿉 뭾遺븯寃 議댁옱븯硫 떎뼇븳 湲곗쟾쓣 넻빐 븣痢좏븯씠癒몃퀝쓽 蹂듭옟븳 諛쒕퀝湲곗쟾뿉 愿뿬븯硫(Wei et al., 2020), 留롮 miRNA媛 뇤 諛쒕떖, 돱윴 遺꾪솕 諛 떆깄뒪 媛냼꽦뿉 빑떖쟻씤 뿭븷쓣 븳떎. miRNA쓽 깉 議곗젅(deregulation) 떆깄뒪 깮꽦, 씠삩 梨꾨꼸 諛쒗쁽, 뿼利 諛 떊寃쏀눜뻾 怨쇱젙쓣 룷븿븯뒗 븣痢좏븯씠癒몃퀝쓣 룷븿븳 떊寃쏀눜뻾꽦 吏덊솚뿉꽌 蹂댁뿬吏꾨떎(Improta-Caria et al., 2020). 븣痢좏븯씠癒몃퀝뿉꽌 蹂寃쎈맂 뿬윭 뿊냼醫 miRNA뒗 APP 泥섎━, 슦 씤궛솕, 誘명넗肄섎뱶由ъ븘 諛 꽭룷옄硫몄궗 愿젴맂 쑀쟾옄瑜 몴쟻쑝濡 븳떎怨 븣젮졇 엳떎(Soares Martins et al., 2021). 씠뒗 씠윭븳 옉 鍮꾩븫샇솕 RNA媛 븣痢좏븯씠癒몃퀝 떊寃쏀눜솕 愿젴맂 湲곗쟾쓣 議곗젅븷 닔 엳쓬쓣 뮮諛쏆묠븳떎.

miRNA뒗 몴쟻 mRNA쓽 3' 鍮꾨쾲뿭 쁺뿭(3' untranslated region, 3'-UTR)뿉 쐞移섑븳 긽蹂댁쟻 遺쐞뿉 寃고빀븯뿬 mRNA 븞젙꽦怨 쟾궗쓽 議곗젅 諛 踰덉뿭쓣 뼲젣븯嫄곕굹 遺꾪빐瑜 쑀룄븳떎. miRNA쓽 1李 怨쇱젙 miRNA媛 빑뿉꽌 RNA 以묓빀슚냼 II/III뿉 쓽빐 pri-miRNA씪怨 븯뒗 겙 RNA 쟾援ъ껜濡 쟾궗맂떎. pri-miRNA뒗 RNase III 슚냼 Drosha DiGeorge 利앺썑援 뿼깋泥 쁺뿭 8 떒諛깆쭏쓽 2媛 subunit 諛 SRp20(젒빀 씤옄)쓽 1媛 subunit 蹂듯빀泥댁쓽 슚냼 옉슜뿉 쓽빐 pre-miRNA (precursor miRNA) 쟾궗泥댁씤 빟 70媛쒖쓽 돱겢젅삤씠뱶 援ъ“씤 뿤뼱 猷⑦봽 援ъ“濡 젅떒맂떎. 洹몃윴 떎쓬 pre-miRNA뒗 exportin 5 寃쎈줈瑜 넻빐 꽭룷吏덈줈 닔넚맂떎. miRNA쓽 2李 怨쇱젙 꽭룷吏덉뿉꽌 pre-miRNA쓽 뿤뼱 猷⑦봽媛 떎瑜 RNase III 슚냼씤 Dicer 諛 TAR RNA-寃고빀 떒諛깆쭏(TRBP)쓣 궗슜븯뿬 miRNA瑜 씠以묒껜 援ъ“濡 泥섎━ 썑 Argonaute (Ago) 떒諛깆쭏怨 寃고빀븳떎. 꽦닕븳 miRNA뒗 Ago-miRNA 蹂듯빀泥대 몴쟻 mRNA濡 蹂대궦떎. Ago-miRNA 蹂듯빀泥대뒗 泥댁븸뿉꽌 留ㅼ슦 븞젙쟻씠湲 븣臾몄뿉 諛쒗쁽릺뒗 miRNA뒗 듅젙 옣湲 諛 蹂묐━ 쁽긽쓣 諛섏쁺븷 닔 엳떎. 씠윭븳 씠쑀濡 miRNA뒗 씠긽쟻씤 諛붿씠삤留덉빱濡 씠슜맆 닔 엳쓬쓣 젣떆븯怨좎옄 븳떎(Wu et al., 2020; Jaber et al., 2019; Madadi et al., 2019; Swarbrick et al., 2019; Kumar and Reddy, 2016). 븳렪, miRNA뒗 꽭룷 쇅 怨듦컙뿉꽌 誘몄꽭냼룷濡 罹≪뒓솕맂 삎깭濡 遺꾨퉬릺嫄곕굹 냼룷媛 뾾뒗 삎깭濡 諛⑹텧맂떎. 洹몃윴 떎쓬 떒諛깆쭏 삉뒗 떎瑜 솕빀臾쇨낵 寃고빀맂떎. miRNA媛 꽭룷 쇅 닚솚 깮泥 쑀泥대줈 씠룞븯뒗 諛⑸쾿뿉뒗 5媛吏媛 엳떎. 泥レ㎏濡 non-vesicle 삎깭쓽 怨좊룄 吏떒諛깆쭏(HDL) 엯옄뿉 寃고빀븳떎. 몮吏몃줈 Ago2 떒諛깆쭏怨 蹂듯빀泥대 삎꽦븳떎. 뀑吏몃줈 뿊냼醫 궡뿉 罹≪뒓솕맂떎. 꽬吏몃줈 誘몄꽭냼룷(micro-vesicles, MVs)뿉 罹≪뒓솕맂떎. 留덉留됱쑝濡, 꽭룷 궗硫몄껜뿉 異뺤쟻맂떎. 뿊냼醫怨 MV뿉 罹≪뒓솕맂 miRNA뒗 DNA, RNA 諛 떒諛깆쭏쓽 꽭룷 궡 넻떊 諛 닔넚쓣 珥됱쭊븳떎. miRNA쓽 빟 90% 젙룄뒗 Ago2 떒諛깆쭏怨 寃고빀븯뒗 MV뿉꽌 諛쒓껄맂떎. Ago2 떒諛깆쭏怨 寃고빀븯뒗 miRNA뒗 깮泥 쑀泥댁뿉꽌 Ago 떒諛깆쭏쓽 넂 븞젙꽦쑝濡 씤빐 nuclease媛 뭾遺븳 솚寃쎌뿉 궡꽦쓣 媛뽯뒗떎. 뜑슧씠 Ago2 떒諛깆쭏 븣痢좏븯씠癒몃퀝쓣 鍮꾨’븳 떊寃쏀눜뻾꽦 吏덊솚씠 엳뒗 궗엺쓽 꽭룷吏덉뿉꽌 諛쒓껄릺뒗 miRNA 떒諛깆쭏 蹂듯빀泥댁쓽 씪遺瑜 삎꽦븯怨, miRNA뿉 뜑 留롮 븞젙꽦쓣 젣怨듯븯뿬 miRNA媛 몴쟻 遺쐞뿉 寃고빀븯뒗뜲 룄쓣 以떎(Kumar and Reddy, 2016). 몴쟻 씪諛섏쟻쑝濡 3'-UTR뿉 쐞移섑븳 miRNA miRNA 諛섏쓳 슂냼(miRNA responsive elements, MREs) 궗씠쓽 뿼湲곗뙇쓣 넻빐 寃고빀븳떎(Ghini et al., 2018). 씎誘몃∼寃뚮룄, 룷쑀룞臾쇱쓽 뇤 留앸쭑뿉 엳뒗 떒씪 mRNA 3'-UTR 뿬윭 miRNA 寃고빀 遺쐞 몴쟻쓣 媛吏 닔 엳쑝硫, 떒씪 miRNA뒗 븯굹 씠긽쓽 mRNA 몴쟻쓣 媛吏 닔 엳떎. 뇤쓽 miRNA-mRNA 꽕듃썙겕瑜 넻븳 쑀쟾쟻 諛 썑꽦 쑀쟾븰쟻 떊샇 쟾떖 뿬윭 븣痢좏븯씠癒몃퀝 愿젴 뇤 떊샇 떆뒪뀥 諛 궗 寃쎈줈뿉꽌 몴쁽릺硫, 씠뒗 miRNA-mRNA 떆뒪뀥씠 諛붿씠삤留덉빱濡쒖꽌 쑀슜븯寃 궗슜맆 닔 엳쓬쓣 떆궗븳떎(Zhao et al., 2020; Lukiw et al., 2020).

湲곗〈뿉 蹂닿퀬맂 븣痢좏븯씠癒몃퀝 뿰援ъ뿉 뵲瑜대㈃ miRNA뒗 씤媛 吏덈퀝쓽 쑀쟾옄, 떒諛깆쭏 諛쒗쁽 諛 몴쁽삎 蹂솕瑜 議곗젅븯뒗 뜲 룄씠 릺硫, miRNA뒗 떎뼇븳 蹂묐━븰쟻 긽깭쓽 諛쒕떖뿉 湲곗뿬븳떎怨 븣젮졇 엳떎(Amakiri et al., 2019). 紐뉖챺 븣痢좏븯씠癒몃퀝怨 愿젴맂 miRNA쓽 湲곕뒫뿉 빐꽌 궡렣蹂닿퀬옄 븳떎(Table 1).

AD-related miRNAs and their targets and responses

Direction of change miRNA Targets Responses
Up-regulated miR-149-5p KAT8 Decline APP & Aβ
miR-485-3p AKT3 Neuro-inflammation
miR-455-3p 3'-UTR of APP Aβ production
miR-501-3p - DNA replication, mitosis
miR-135a - APP & β-secretase regulation
miR-384 - APP & β-secretase regulation
miR-144-3p MRE with the 3'-UTR of ADAM10 mRNA Negative regulator of a disintegrin and metalloprotease 10
miR-151-3p DAPK-1, TP53 Enhance the anti-apoptotic and anti-oxidant effects
miR-125b BACE1 Aβ neurotoxicity mitigation
Down-regulated miR-15b - Protect anti-Aβ
miR-219 3'-UTR of mRNA Tau toxicity control
miR-193b - APP & β-secretase regulation
miR-101-3p 3'-UTR of APP Negative regulator of APP
miR-153-3p 3'UTR of APP & APLP2 Post-transcriptional regulation of APP and APLP2
miR-381-3p LRRC4 Regulate SDF-1/CXCR-4 signaling pathway
miR-383-5p PPARγ Regulate post-transcriptional levels of PPARγ expression

Each miRNA regulates the response of the target substance in Alzheimer's disease. APP; amyloid precursor protein, Aβ; beta-amyloid peptide, 3-'UTR; 3' untranslated region, MRE; miRNA recognition element, APLP2; amyloid precursor-like protein 2, SDF-1; stromal cell-derived factor-1, CXCR-4; CXC chemokine receptor-4, PPARγ; peroxisome proliferator-activated receptor γ. KAT8; Lysine acetyltransferase 8, AKT3; AKT serine/threonine Kinase 3, ADAM10; a disintegrin and metalloprotease 10, DAPK-1; death-associated protein kinase 1, BACE1; beta-site APP cleaving enzyme 1, LRRC4; leucine-rich repeat C4 protein



Shi et al.뒗 miR-132쓽 쇅씤꽦 삎吏덇컧뿼씠 떆뿕愿 궡 넀긽맂 HT-22 꽭룷뿉꽌 GSK-3β쓽 諛쒗쁽쓣 븯뼢 議곗젅븷 닔 엳쓬쓣 諛앺깉떎(Shi et al., 2020). 삉븳 Deng et al.뒗 miR-132媛 p38 떊샇 쟾떖 寃쎈줈瑜 넻빐 AD 伊먯쓽 뇤 議곗쭅뿉꽌 Nitric oxide synthase (iNOS)쓽 諛쒗쁽쓣 뼲젣븯怨 궛솕 뒪듃젅뒪瑜 媛먯냼떆궎硫 씤吏 湲곕뒫쓣 媛쒖꽑븳떎怨 諛앺깉떎(Deng et al., 2020). Liu et al.뒗 miR-132媛 HMGA2쓽 諛쒗쁽쓣 몴쟻솕 諛 뼲젣븷 닔 엳怨, PI3K/AKT 寃쎈줈쓽 諛쒗쁽쓣 긽뼢 議곗젅븯뿬 AD 留덉슦뒪쓽 뇤 넀긽쓣 셿솕븷 닔 엳떎怨 蹂닿퀬뻽떎(Liu et al., 2021). 씠뒗 miR-132媛 AD쓽 깉濡쒖슫 移섎즺 몴쟻씠 맆 닔 엳쓬쓣 蹂댁뿬以떎.

Vergallo et al.뒗 miR-15b媛 Aβ 뼇꽦 媛쒖껜뿉꽌 븯뼢 議곗젅릺뿀怨, miR-125b뒗 AD 솚옄쓽 痢〓몢뿽 떊뵾吏덉뿉꽌 긽뼢 議곗젅릺뿀떎怨 諛앺삍떎. miR-125b뒗 BACE1 떒諛깆쭏怨 寃고빀븯뿬 BACE1쓽 諛쒗쁽 닔以쓣 뼲젣븯怨 Aβ뿉 쓽븳 떊寃쎈룆꽦쓣 셿솕븳떎. BACE1 蹂듦뎄뒗 Aβ-쑀룄 떊寃쎈룆꽦뿉 븳 miR-125b쓽 슚怨쇰 뼲젣븳떎. 寃곌낵쟻쑝濡, 蹂 끉臾몄 뼲젣맂 miR-125b媛 BACE1 諛쒗쁽쓣 媛먯냼떆耳 AD 諛쒕떖쓣 뼲젣븷 닔 엳쓬쓣 蹂댁뿬以떎(Vergallo et al., 2021).

Chen et al.뒗 miR-149-5p媛 AD 솚옄 諛 AD 꽭룷 紐⑤뜽쓽 삁옣뿉꽌 媛곴컖 쑀쓽븯寃 利앷븯쓬쓣 諛앺삍떎. miR-149-5P뒗 KAT8 諛쒗쁽 諛 H4K16 븘꽭떥솕 議곗젅쓣 넻빐 293/APPsw 꽭룷뿉꽌 APP 諛 Aβ 닔以쓣 媛먯냼떆耳 293/APPsw 꽭룷뿉 떊寃쎈룆꽦 슚怨쇰 굹깉떎. 삉븳 H4K16 븘꽭떥솕쓽 KAT8 쑀룄 利앷뒗 엳뒪넠 愿젴 씠吏덉뿼깋吏 援ъ“瑜 蹂寃쏀븯뿬 떎뼇븳 AD 愿젴 쑀쟾옄 쟾궗瑜 議곗젅븯怨 떊寃쎈룆꽦 APP 泥섎━瑜 뼲젣븷 닔 엳떎. 寃곕줎쟻쑝濡, 蹂 뿰援щ뒗 miR-149-5p 諛쒗쁽쓣 媛먯냼떆耳 AD쓽 蹂묐━븰쟻 吏꾪뻾쓣 빟솕떆궎뒗 깉濡쒖슫 젒洹쇰쾿쓣 젣븞븳떎(Chen et al., 2020).

Guo et al.뒗 DAPK-1怨 TP53쓣 紐⑤몢 몴쟻쑝濡 븯뒗 miR-151-3p瑜 꽑蹂꾪뻽떎. DAPK-1怨 TP53 뇤쓽 AD 愿젴 떊寃 蹂꽦怨 뿰愿릺뼱 엳뼱 AD쓽 옞옱쟻씤 移섎즺 몴쟻쑝濡 젣븞맂떎. 씠 뿰援щ뒗 DAPK-1 諛 p53쓣 몴쟻쑝濡 븯뒗 miR-151-3p瑜 利앷떆耳곗쑝硫, 씠뒗 Aβ뿉 븳 Dex쓽 빆-꽭룷옄硫몄궗 諛 빆궛솕 슚怨쇰 뼢긽떆耳곕떎(Guo et al., 2021).

Yu et al.뒗 AD 솚옄 AD 紐⑤뜽뿉꽌 miR-485-3p쓽 諛쒗쁽 닔以씠 嫄닿컯 議곌뎔怨 鍮꾧탳븯뿬 긽뼢 議곗젅릺뿀쓬쓣 諛앺깉떎. miR-485-3p뒗 AKT3瑜 몴쟻븯뿬 miR-485-3p쓽 끃떎슫(knockdown)씠 떊寃 꽭룷 利앹떇쓣 珥됱쭊븯怨, AKT3瑜 留ㅺ컻븷 닔 엳뒗 떊寃 꽭룷 궗硫 諛 떊寃 뿼利앹쓣 뼲젣븳떎. 뵲씪꽌 씠 뿰援щ뒗 miR-485-3p媛 떊寃 꽭룷 깮議대젰쓣 媛먯냼떆궎怨 떊寃 뿼利앹쓣 媛쒖꽑븿쑝濡쒖뜥 AD뿉꽌 떊寃쎈룆꽦 뿭븷쓣 븷 닔 엳쑝硫 移섎즺 몴쟻씠 맆 닔 엳떎怨 젣븞븳떎. 寃곌낵쟻쑝濡, 깉濡쒖슫 吏꾨떒 諛붿씠삤留덉빱 AD 移섎즺뿉 븳 옞옱쟻씤 移섎즺 몴쟻뿉 븳 利앷굅瑜 젣怨듯븷 닔 엳떎(Yu et al., 2021).

Santa-Maria et al.뒗 miR-219媛 AD 諛 1李 뿰졊 愿젴 슦蹂묒쬆뿉꽌 븯뼢 議곗젅맖쓣 諛앺깉떎. miR-219뒗 깮泥 궡뿉꽌 슦 룆꽦쓣 議곗젅븯硫 슦 mRNA쓽 吏곸젒쟻씤 긽샇 옉슜쓣 넻빐 쟾궗 썑 닔以뿉꽌 슦 諛쒗쁽쓣 議곗젅븳떎. 룷쑀瑜 꽭룷 紐⑤뜽뿉꽌 miR-219媛 슦 떒諛깆쭏 mRNA쓽 3'-UTR뿉 吏곸젒 寃고빀빐 쟾궗 썑 슦 빀꽦쓣 뼲젣븳떎뒗 寃껋쓣 諛쒓껄뻽떎. 씠윭븳 寃곌낵뒗 miR-219뿉 쓽븳 슦 떒諛깆쭏쓽 移⑤У씠 떊寃쎌썝꽟쑀쓽 蹂꽦 룞븞 援먮맆 닔 엳뒗 議곗젅 硫붿빱땲利섏엫쓣 굹궡硫 씠 議곗젅 寃쎈줈媛 AD 슦蹂묒쬆뿉 븳 移섎즺젣 媛쒕컻뿉 쑀슜븷 닔 엳쓬쓣 굹궦떎(Santa-Maria et al., 2015).

Kumar et al.뒗 miR-455-3p媛 AD 솚옄뿉꽌 긽뼢 議곗젅맖쓣 諛앺깉떎. 寃뚮떎媛 AD뿉꽌쓽 꽟쑀紐⑥꽭룷 諛 由쇳봽紐⑥꽭룷뿉꽌 利앷맂 miR-455-3p媛 AD쓽 뇤 諛 留먯큹꽭룷뿉꽌 쟾삎쟻씤 듅吏뺤엫쓣 굹궦떎. 삉븳 APP 쑀쟾옄쓽 3'-UTR뿉 엳뒗 miR-455-3p쓽 몢 媛吏 옞옱쟻씤 寃고빀 遺쐞媛 APP 쟾泥 湲몄씠쓽 議곗젅뿉 愿뿬븷 닔 엳怨, miR-455-3p媛 APP 泥섎━ 諛 븘諛濡쒖씠뱶 踰좏 깮궛뿉 쁺뼢쓣 誘몄튌 寃껋쑝濡 삁痢≫뻽떎(Kumar and Reddy, 2018). Kumar et al.쓽 떎瑜 뿰援ъ뿉꽌뒗 miR-455-3p媛 꽭룷 깮議댁쓣 利앷떆궎怨 꽭룷 利앹떇쓣 珥됱쭊븳떎怨 諛앺깉떎. 삉븳 miR-455-3p쓽 怨쇰컻쁽씠 APP쓽 C-留먮떒 떒렪씤 쟾泥 湲몄씠 APP 諛쒗쁽쓣 媛먯냼떆궎怨 Aβ-40 諛 Aβ-42 닔以쓣 媛먯냼떆궓떎怨 諛앺삍떎. miR-455-3p쓽 닔以씠 利앷븯硫 誘명넗肄섎뱶由ъ븘 깮빀꽦, 誘명넗肄섎뱶由ъ븘 쑖빀 諛 떆깄뒪 쑀쟾옄룄 利앷븳떎. 씠윭븳 諛쒓껄 鍮꾩젙긽쟻씤 APP 泥섎━뿉꽌 miR-455-3p쓽 誘명넗肄섎뱶由ъ븘 깮빀꽦/뿭븰 諛 떆깄뒪 媛냼꽦쓽 議곗젅씠 AD瑜 떇蹂꾪븯湲 쐞븳 洹以묓븳 옞옱쟻 遺꾩옄엫쓣 떆궗븳떎(Kumar et al., 2019).

Hara et al.뒗 miR-501-3p 닔以씠 AD 솚옄쓽 삁泥뿉꽌뒗 븯뼢 議곗젅릺뒗 諛섎㈃ 뇤 닔以뿉꽌뒗 젙긽씤 鍮 쁽븯寃 긽뼢 議곗젅맖쓣 諛앺깉떎. 삉븳 諛곗뼇맂 꽭룷뿉꽌 miR-501-3p 怨쇰컻쁽씠 DNA 蹂듭젣 諛 쑀궗遺꾩뿴 꽭룷 二쇨린쓽 깮臾쇳븰쟻 怨쇱젙뿉꽌 128媛 쑀쟾옄쓽 븯뼢 議곗젅쓣 쑀룄븳떎뒗 寃껋쓣 諛쒓껄뻽떎. 씠뒗 꽭룷 궗硫몃줈 씠뼱吏뒗 쑀궗遺꾩뿴 썑 돱윴쓽 遺쟻젅븳 꽭룷 二쇨린 옱吏꾩엯씠 AD 뇤뿉꽌 끂씤꽦 뵆씪겕 諛 떊寃쎌꽟쑀 떎諛쒖쓽 諛쒕떖濡 씠뼱吏뒗 珥덇린 吏뺥썑엫쓣 굹궦떎. 寃곕줎쟻쑝濡, 蹂 뿰援щ뒗 삁泥 miR-501-3p媛 AD쓽 吏꾪뻾쓣 諛섏쁺븯뒗 깉濡쒖슫 吏몴엫쓣 떆궗븳떎(Hara et al., 2017).

씠 쇅뿉룄 Yang et al.뒗 miR-135a 諛 miR-384媛 븣痢좏븯씠癒몃퀝뿉꽌 쑀쓽븯寃 利앷븯怨, miR-193b뒗 쑀쓽븯怨 媛먯냼뻽떎怨 諛앺삍떎(Yang et al., 2018). Zhou et al. miR-101-3p, miR-153-3p, miR-381-3p, miR-383-5p뒗 븣痢좏븯씠癒몃퀝뿉꽌 븯뼢 議곗젅릺뿀怨 miR-144-3p뒗 긽뼢 議곗젅릺뿀떎怨 諛앺삍떎(Zhou et al., 2019).

4. 寃곕줎

씠 끉臾몄 븣痢좏븯씠癒몃퀝뿉꽌 媛옣 빑떖쟻씤 蹂묐━ 쁽긽쑝濡 븣젮졇 엳뒗 踰좏 븘諛濡쒖씠뱶 떒諛깆쭏쓽 異뺤쟻怨 뜑遺덉뼱 슦 떒諛깆쭏쓽 怨쇱씤궛솕뿉 빐꽌 꽕紐낇뻽떎. 洹몄 룞떆뿉 쁽옱 뿰援щ릺怨 엳뒗 븣痢좏븯씠癒몃퀝怨 miRNA쓽 긽愿愿怨꾨 뿰援ы븳 寃곌낵瑜 젣떆븿쑝濡쒖뜥 miRNA媛 蹂듭옟븳 솚寃쎌뿉꽌 議곗젅릺뒗 븣痢좏븯씠癒몃퀝쓽 吏꾨떒 諛 移섎즺젣濡쒖꽌 깉濡쒖슫 諛붿씠삤留덉빱媛 맆 닔 엳쓬쓣 꽕紐낇븯怨좎옄 븯떎.

쁽옱 븣痢좏븯씠癒몃퀝쓣 移섎즺븷 닔 엳뒗 洹쇰낯쟻씤 移섎즺젣뒗 떆옣뿉 異쒖떆릺뼱 엳吏 븡怨 엳떎. 븘諛濡쒖씠뱶 踰좏굹 슦 蹂묒쬆뿉 븳 뿰援ш 留롮씠 吏꾪뻾릺硫댁꽌 洹몄 愿젴맂 빆泥댁쓽빟뭹쓽 媛쒕컻씠 二쇰 씠猷⑤㈃꽌 留롮 뿰援ш 릺怨 엳떎. 븯吏留, 洹몄뿉 뵲瑜 遺옉슜 臾몄젣濡 쁽옱 뿰援ъ뿉 留롮 뼱젮쓣 寃り퀬 엳뒗 떎젙씠떎. 理쒓렐뿉뒗 슦 떒諛깆쭏쓽 議곗젅뿉 愿뿬븯뒗 븞떚꽱뒪 삱由ш퀬돱겢젅삤씠뱶(anti-sense oligonucleotide, ASO)瑜 씠슜빐꽌 엫긽 1긽뿉 뱾뼱媛뒗 븣痢좏븯씠癒몃퀝 移섎즺젣 썑蹂대Ъ吏덉씠 떆옣뿉 굹삤硫댁꽌 빆泥 쓽빟뭹씠 븘땶 쑀쟾옄 移섎즺젣 떆옣씠 깉濡寃 뼚삤瑜닿퀬 엳떎. 뿬湲곗꽌 ASO뒗 mRNA 긽蹂댁쟻쑝濡 寃고빀빐꽌 듅젙 떒諛깆쭏쓽 諛쒗쁽쓣 議곗젅븷 닔 엳뒗 듅吏뺤쓣 媛뽯뒗떎. 吏湲덇퉴吏뒗 吏덈퀝쓣 씪쑝궎뒗 듅젙 떒諛깆쭏쓣 몴쟻쑝濡 븯뒗 遺꾩옄솕빀臾쇱씠굹 諛붿씠삤濡쒖쭅뒪 빟臾쇱쓽 媛쒕컻씠 二쇰 씠猷⑥뿀떎硫, 씠뿉 뵲瑜 遺옉슜 諛 빟슚뒫 誘몃퉬濡 씤빐 mRNA굹 miRNA瑜 씠슜븳 쑀쟾옄 移섎즺젣濡 깉濡쒖슫 媛쒕컻쓣 떆룄븯뒗 떆옣쓽 쓲由꾩씠 愿李곕릺怨 엳떎(Cummings et al., 2020).

븣痢좏븯씠癒몃퀝 蹂듭옟븳 솚寃쎌뿉꽌 뿬윭 蹂묐━ 쁽긽쓣 媛吏怨 엳떎. 옄뒗 씠윭븳 蹂듭옟븳 蹂묐━쁽긽쓣 議곗젅븷 닔 엳뒗 媛옣 쑀젰븳 썑蹂댁젣濡 miRNA瑜 湲곕컲쑝濡 븯뒗 쑀쟾옄 移섎즺젣瑜 젣떆븯怨좎옄 븳떎. miRNA뒗 븵꽌 궡렣蹂댁븯벏씠 뿬윭 mRNA瑜 議곗젅븿쑝濡 씤빐 뿬윭 蹂묐━ 쁽긽뿉 愿뿬븿쓣 넻빐 蹂듭옟븳 꽭룷솚寃쎌쓣 議곗젅븷 닔 엳쓣 寃껋쑝濡 깮媛곷맂떎. 理쒓렐뿉뒗 Koh et al.씠 miR-485-3p媛 븘諛濡쒖씠뱶 踰좏 떒諛깆쭏 諛 슦쓽 怨쇱씤궛솕瑜 議곗젅븯怨, 궛솕쟻 뒪듃젅뒪 諛 꽭룷뿼利앹쓣 議곗젅븯怨, 뜑슧씠 뻾룞蹂솕源뚯룄 쉶蹂듭떆궓떎뒗 怨좊Т쟻씤 뿰援ш껐怨쇰 젣떆븯怨 엳뼱, miRNA-485-3p媛 븣痢좏븯씠癒몃퀝쓽 吏꾨떒 諛 移섎즺뿉 궗슜맆 닔 엳쓬쓣 떆궗븯怨 엳떎(Koh et al., 2021).

miRNA 湲곕컲 移섎즺젣쓽 뿰援щ뒗 쁽옱룄 솢諛쒗븯寃 吏꾪뻾씠 릺怨 엳怨, 븵쑝濡쒕룄 留롮씠 吏꾪뻾씠 릺뼱빞 븯寃좎留, 洹쇰낯쟻씤 移섎즺젣媛 뾾뒗 蹂듭옟븳 븣痢좏븯씠癒몃퀝쓣 移섎즺븷 닔 엳뒗 怨좊Т쟻씤 移섎즺諛⑹븞씠 맆 닔 엳쓬쓣 씠 끉臾몄쓣 넻빐 젣떆븯怨좎옄 븳떎.

ACKNOWLEDGEMENT

None.

CONFLICT OF INTEREST

The authors declare no competing interests.

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