裴昕嶼 陳宗浩 周 宇

廣東醫(yī)科大學(xué)附屬醫(yī)院消化內(nèi)科(524001)

LncRNA與炎癥性疾病關(guān)系的研究進(jìn)展*

裴昕嶼 陳宗浩 周 宇#

廣東醫(yī)科大學(xué)附屬醫(yī)院消化內(nèi)科(524001)

長鏈非編碼RNA(lncRNA)是一類缺少完整開放閱讀框(ORF)的非編碼RNA，在細(xì)胞增殖、分化和凋亡等生物學(xué)過程中發(fā)揮重要作用。目前研究發(fā)現(xiàn)，lncRNA在炎癥反應(yīng)和炎癥性疾病中表達(dá)異常，可通過調(diào)節(jié)多種基因表達(dá)和信號(hào)通路激活，參與炎癥性疾病的發(fā)生、發(fā)展。本文就lncRNA與炎癥性疾病關(guān)系的研究進(jìn)展作一綜述。

炎癥性疾病； 長鏈非編碼RNA； 炎癥； 炎性腸疾病

Correspondenceto: ZHOU Yu, Email: ahdg2005@126.com

AbstractLong non-coding RNA (lncRNA) is a non-coding RNA which lacks a complete open reading frame (ORF) and plays an important role in biological processes such as cell proliferation, differentiation and apoptosis. At present, expression of lncRNA has been found to be abnormal in inflammatory reaction and inflammatory diseases. It might be involved in the development and progression of inflammatory diseases via regulating the expression of multiple genes and activation of signaling pathways. This article reviewed the progress in study on relationship between lncRNA and inflammatory diseases.

KeywordsInflammatory Disease; Long Non-Coding RNA; Inflammation; Inflammatory Bowel Diseases

炎癥是由多種炎癥細(xì)胞和炎癥因子共同參與的重要病理過程，是機(jī)體對(duì)病原微生物感染、創(chuàng)傷、變態(tài)反應(yīng)等發(fā)生的組織細(xì)胞反應(yīng)。長鏈非編碼RNA(lncRNA)是一類缺少完整開放閱讀框(ORF)的非編碼RNA，對(duì)基因表達(dá)、細(xì)胞分化、細(xì)胞凋亡乃至疾病(如炎癥、腫瘤)均有重要影響，在基因轉(zhuǎn)錄和轉(zhuǎn)錄后調(diào)控等過程中扮演重要角色，如X染色體失活、基因組印記、干細(xì)胞多能性、癌癥轉(zhuǎn)移、動(dòng)脈粥樣硬化等[1]。lncRNA在炎癥性疾病中異常表達(dá)，與多種炎癥相關(guān)基因表達(dá)和信號(hào)通路活化有關(guān)。lncRNA對(duì)炎癥反應(yīng)的調(diào)節(jié)作用為炎癥性疾病的診治提供了新思路。本文就lncRNA與炎癥性疾病關(guān)系的研究進(jìn)展作一綜述。

一、lncRNA的結(jié)構(gòu)和功能

lncRNA是一類長度大于200 nt的非編碼RNA，因缺少完整的ORF而無蛋白質(zhì)編碼功能。據(jù)報(bào)道，lncRNA的轉(zhuǎn)錄與mRNA類似，多數(shù)由RNA聚合酶Ⅱ介導(dǎo)，且通常包含多聚腺苷酸化信號(hào)序列；部分lncRNA轉(zhuǎn)錄可由RNA聚合酶Ⅲ介導(dǎo)[2]。相比蛋白質(zhì)編碼基因，大多數(shù)lncRNA的保守性低于mRNA，但并不一定意味其缺乏功能。很多l(xiāng)ncRNA的一級(jí)結(jié)構(gòu)和二級(jí)結(jié)構(gòu)與其特定功能相關(guān)。如lncRNA MALAT1的3’末端有一個(gè)類似于tRNA的結(jié)構(gòu)，使其在RNA聚合酶Ⅱ作用下可形成豐富的轉(zhuǎn)錄產(chǎn)物，該結(jié)構(gòu)被視為基因組標(biāo)簽[3]。SPRY4-IT1是來源于SPRY4基因內(nèi)含子的癌癥相關(guān)lncRNA，其二級(jí)結(jié)構(gòu)可包含多個(gè)發(fā)夾結(jié)構(gòu)，與SPRY4基因在黑色素細(xì)胞瘤中的轉(zhuǎn)錄和翻譯密切相關(guān)[4]。

lncRNA通過多種機(jī)制參與蛋白編碼基因和表觀遺傳基因的表達(dá)調(diào)控，如表觀遺傳修飾、可變剪接、轉(zhuǎn)錄后和翻譯調(diào)控等[2]。lncRNA可跨越下游蛋白編碼基因的啟動(dòng)子區(qū)域，干擾轉(zhuǎn)錄因子與DNA啟動(dòng)子結(jié)合，從而抑制基因表達(dá)[5]。lncRNA可誘導(dǎo)DNA甲基化和異染色質(zhì)形成，導(dǎo)致腫瘤抑制基因沉默[6]。lncRNA可通過結(jié)合轉(zhuǎn)錄因子或激活輔助蛋白來抑制基因表達(dá)[7]，也可通過激活轉(zhuǎn)錄因子或誘導(dǎo)蛋白質(zhì)三聚體形成來促進(jìn)靶基因表達(dá)[8]。lncRNA不僅可通過與輸入蛋白相互作用來調(diào)節(jié)轉(zhuǎn)錄因子的亞細(xì)胞定位，還可作為前體細(xì)胞小分子RNA發(fā)揮功能，或通過結(jié)合小分子RNA來調(diào)節(jié)其活動(dòng)[9]。此外，lncRNA還可通過影響染色質(zhì)結(jié)構(gòu)來抑制mRNA功能和非編碼轉(zhuǎn)錄過程，從而調(diào)控基因活動(dòng)，如核小體定位和染色體循環(huán)等[10]。

二、lncRNA與炎癥細(xì)胞和炎癥因子的關(guān)系

lncRNA廣泛表達(dá)于單核細(xì)胞、巨噬細(xì)胞、樹突細(xì)胞(DC)、中性粒細(xì)胞、T細(xì)胞和B細(xì)胞中，參與機(jī)體的炎癥反應(yīng)過程。

1. lncRNA與炎癥細(xì)胞的關(guān)系：lncRNA lnc-DC可在DC中特異性表達(dá)，參與調(diào)控DC分化、DC表面協(xié)同刺激分子(如CD40、CD80和HLA-DR等)表達(dá)以及誘導(dǎo)外源性CD4+T細(xì)胞增殖和炎癥細(xì)胞因子產(chǎn)生等[11]。因此，lncRNA在炎癥介質(zhì)產(chǎn)生以及炎癥細(xì)胞分化、遷移等多種生物學(xué)過程中起有重要作用。

2. lncRNA與炎癥因子的關(guān)系：近年來，lncRNA在炎癥性疾病中的重要作用成為研究焦點(diǎn)。系統(tǒng)性紅斑狼瘡(SLE)患者的脂多糖(LPS)可通過激活p38信號(hào)通路，誘導(dǎo)lncRNA NEAT1在單核細(xì)胞中異常高表達(dá)；通過抑制NEAT1表達(dá)，可顯著降低LPS誘導(dǎo)的趨化因子和細(xì)胞因子表達(dá)[12]。lncRNA Lethe能直接與NF-κB異二聚體亞單位RelA結(jié)合，抑制NF-κB的DNA結(jié)合活性，因而Lethe可作為腫瘤壞死因子(TNF)-α通路的負(fù)反饋調(diào)節(jié)因子，調(diào)控炎癥反應(yīng)[13]。lncRNA THRIL是TNF-α相關(guān)的免疫調(diào)節(jié)lncRNA，其表達(dá)在川崎病急性反應(yīng)期顯著降低，說明THRIL可能通過調(diào)控炎癥因子表達(dá)，參與疾病進(jìn)程[14]。lncRNA lnc-IL7R由LPS誘導(dǎo)產(chǎn)生，可通過抑制TLR2和TLR4受體激動(dòng)劑表達(dá)，在病原體感染免疫應(yīng)答和自身免疫性炎癥反應(yīng)中發(fā)揮重要作用。lncRNA MALAT1可抑制NF-κB的DNA結(jié)合活性，減少炎癥細(xì)胞因子產(chǎn)生，下調(diào)自身免疫炎癥反應(yīng)；通過敲除MALAT1可上調(diào)LPS誘導(dǎo)的TNF-α和IL-6表達(dá)[15]。lncRNA-CD244在結(jié)核分枝桿菌感染的SCID小鼠CD8+T細(xì)胞中表達(dá)增加，從而抑制IFN-γ和TNF-α等促炎細(xì)胞因子產(chǎn)生；通過下調(diào)lncRNA-CD244可逆轉(zhuǎn)該效應(yīng)并減輕感染，說明lncRNA-CD244可參與機(jī)體抗結(jié)核感染的免疫應(yīng)答，并可能作為潛在的治療靶點(diǎn)[16]。

三、lncRNA與炎癥性疾病的關(guān)系

1. lncRNA與炎癥性腸病(IBD)的關(guān)系：lncRNA在胃腸道疾病中的研究較少，可能在炎癥級(jí)聯(lián)反應(yīng)中起有重要作用。IBD是一種慢性炎癥性腸道疾病，包括潰瘍性結(jié)腸炎(UC)和克羅恩病(CD)。Mirza等[17]的研究發(fā)現(xiàn)，活動(dòng)期UC和CD患者中分別有745和438個(gè)lncRNA存在差異性表達(dá)，而緩解期患者中分別為19和12個(gè)。lncRNA ANRIL在多種疾病中發(fā)揮重要調(diào)控作用，其表達(dá)在UC和CD中均明顯下調(diào)，但作用尚不明確。Wu等[18]的研究結(jié)果顯示，多數(shù)lncRNA位于細(xì)胞核，UC患者中分別有329個(gè)lncRNA表達(dá)上調(diào)和126個(gè)lncRNA表達(dá)下調(diào)，其中活動(dòng)期UC患者lncRNA BC012900在刺激因子作用下表達(dá)顯著上調(diào)。有研究[19-20]發(fā)現(xiàn)，過表達(dá)lncRNA PlncRNA-1對(duì)腸黏膜屏障有保護(hù)作用，而過表達(dá)lncRNA H19可破壞腸黏膜屏障，加速UC進(jìn)展。Chen等[21]的研究發(fā)現(xiàn)，CD患者中分別有1 211個(gè)lncRNA表達(dá)上調(diào)和777個(gè)lncRNA表達(dá)下調(diào)，其中l(wèi)ncRNA DQ786243表達(dá)上調(diào)，可通過調(diào)節(jié)CREB和Foxp3表達(dá)來影響T細(xì)胞功能[22]。上述研究結(jié)果表明lncRNA可能參與IBD發(fā)生、發(fā)展。

2. lncRNA與胃食管炎癥性疾病的關(guān)系：幽門螺桿菌(Hp)可導(dǎo)致慢性胃炎、消化道潰瘍等疾病，其具體機(jī)制尚不清楚。目前已知少數(shù)lncRNA在Hp感染中異常表達(dá)，包括23個(gè)表達(dá)上調(diào)和21個(gè)表達(dá)下調(diào)[23]。lncRNA的差異性表達(dá)可能是Hp感染誘導(dǎo)免疫應(yīng)答的關(guān)鍵，因此可作為Hp感染慢性胃炎的潛在治療靶點(diǎn)。嗜酸性食管炎(EoE)是一種過敏性炎癥性疾病，lncRNA BANCR在EoE中表達(dá)上調(diào)，通過抑制BANCR可顯著降低IL-13誘導(dǎo)的促炎基因表達(dá)，因此BANCR可能成為EoE的診斷標(biāo)記物和治療新靶點(diǎn)[24]。

3. lncRNA與炎癥性肝臟疾病的關(guān)系：非酒精性脂肪性肝病(NAFLD)是由胰島素抵抗、遺傳易感、自身免疫等因素導(dǎo)致的肝臟疾病。研究[25]表明，lncRNA lnc-JAM2-6表達(dá)與NAFLD嚴(yán)重程度密切相關(guān)，且lnc-JAM2-6的調(diào)控元件包含轉(zhuǎn)錄因子CEBPB的特異性結(jié)合序列，說明lnc-JAM2-6可能參與NAFLD中CEBPB誘導(dǎo)的炎癥反應(yīng)。

4. lncRNA與血管炎癥性疾病的關(guān)系：lncRNA可通過調(diào)節(jié)血管炎癥性疾病患者NF-κB表達(dá)，參與血管動(dòng)脈粥樣硬化和慢性血栓栓塞性肺動(dòng)脈高壓(CTEPH)的發(fā)生、發(fā)展。lncRNA-p21在小鼠動(dòng)脈粥樣硬化模型中表達(dá)下調(diào)，抑制平滑肌細(xì)胞增殖，從而促進(jìn)頸動(dòng)脈損傷后內(nèi)膜新生[26]。此外，lncRNA ANRIL位于CAD基因易感位點(diǎn)9p21.3，可調(diào)控平滑肌細(xì)胞增殖，進(jìn)而參與血管炎癥反應(yīng)。lncRNA(NR036693、NR027783、NR033766和NR001284)在CTEPH中表達(dá)異常，通過分析疾病相關(guān)基因附近的lncRNA有助于了解其在CTEPH中的作用[27]。

5. lncRNA與1型糖尿病(T1DM)的關(guān)系：免疫反應(yīng)介導(dǎo)的炎癥可能是T1DM的發(fā)病機(jī)制之一，中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白(NGAL)可誘導(dǎo)炎癥介質(zhì)表達(dá)，形成T1DM的炎癥微環(huán)境。lncRNA NONMMUT036704表達(dá)在胰島β細(xì)胞株MIN6中明顯增加，推測(cè)其可能通過調(diào)節(jié)NGAL表達(dá)來參與T1DM的發(fā)生、發(fā)展[28]。表皮生長因子受體3(ErbB3)與T1DM中殘余β細(xì)胞功能密切相關(guān)，通過敲除大鼠胰島素瘤細(xì)胞株INS-1E中的ErbB3可誘導(dǎo)細(xì)胞凋亡，而ErbB3表達(dá)與lncRNA NONHSAG011351顯著相關(guān)，推測(cè)后者可能通過調(diào)節(jié)ErbB3表達(dá)來參與INS-1E細(xì)胞凋亡以及T1DM發(fā)生[29]。因此，深入研究lncRNA的功能可能有助于發(fā)現(xiàn)T1DM診治的新靶點(diǎn)。

6. lncRNA與風(fēng)濕性疾病炎癥的關(guān)系：類風(fēng)濕性關(guān)節(jié)炎(RA)的特征是滑膜細(xì)胞增生、血管翳形成、軟骨退化、骨侵蝕和廣泛的血管新生。RA的發(fā)生與多種lncRNA有關(guān)，其中l(wèi)ncRNA NR024118在RA滑膜成纖維細(xì)胞株MH7A中的表達(dá)明顯上調(diào)，可明顯抑制MH7A細(xì)胞增殖，減弱軟組織和骨損傷[30]。紫草醌是治療RA的抗炎藥物，可顯著促進(jìn)NR024118表達(dá)，而NR024118過表達(dá)可逆轉(zhuǎn)紫草醌對(duì)促炎因子的調(diào)控作用，因此推測(cè)紫草醌可通過上調(diào)NR024118來抑制炎癥反應(yīng)，進(jìn)而發(fā)揮其療效。強(qiáng)直性脊柱炎(AS)患者lncRNA AK001085表達(dá)下降，且與疾病活動(dòng)性指標(biāo)呈負(fù)相關(guān)，并受吸煙、運(yùn)動(dòng)和職業(yè)等因素影響，因此AK001085可作為獨(dú)立診斷AS的潛在指標(biāo)[31]。

7. lncRNA與腎臟炎癥性疾病的關(guān)系：轉(zhuǎn)化生長因子-β1(TGF-β1)在腎臟炎癥和纖維化中扮演重要角色，而Smad3是該過程中的關(guān)鍵因子。Zhou等[32]發(fā)現(xiàn)，Smad3-/-小鼠lncRNA Arid2-IR表達(dá)上調(diào)，并可通過激活NF-κB通路導(dǎo)致腎臟病變，因此Arid2-IR可能成為腎臟炎癥性疾病治療的新靶點(diǎn)。研究[33]發(fā)現(xiàn)，在缺氧和細(xì)胞因子刺激下，近端小管上皮細(xì)胞(PTEC) lncRNA(MIR210HG、linc-ATP13A4-8、linc-KIAA1737-2)表達(dá)升高，并參與PTEC損傷和炎癥反應(yīng)過程。在糖尿病大鼠腎小管上皮細(xì)胞和高糖處理的人腎小管上皮細(xì)胞株HK-2中l(wèi)ncRNA MALAT1表達(dá)顯著升高，通過下調(diào)MALAT1水平可抑制HK-2細(xì)胞凋亡以及ELAVL1、NLRP3和IL-1β表達(dá)，以上機(jī)制可能為糖尿病腎病的治療提供新策略[34]。

8. lncRNA與其他慢性炎癥性疾病的關(guān)系：牙周炎患者lncRNA POIR可通過競爭性抑制microRNA-182表達(dá)，下調(diào)靶基因FoxO1表達(dá)，進(jìn)而參與調(diào)控人牙周膜間充質(zhì)干細(xì)胞(hPDLSC)的成骨分化，這一機(jī)制可能為牙周炎治療提供新思路[35]。呼吸道慢性炎癥患者氣管上皮細(xì)胞(AEC)和氣管平滑肌細(xì)胞可分泌促炎介質(zhì)，上調(diào)lncRNA GAS5表達(dá)；通過抑制GAS5表達(dá)可提高糖皮質(zhì)激素活性，從而改善氣管阻力[36]。慢性鼻竇炎合并鼻息肉患者lncRNA存在差異性表達(dá)，其中l(wèi)ncRNA XLOC_010280可調(diào)節(jié)趨化因子配體18(CCL18)表達(dá)以及嗜酸性粒細(xì)胞炎癥反應(yīng)，促進(jìn)炎癥性息肉的發(fā)展[37]。

四、結(jié)語

綜上所述，lncRNA與多種炎癥性疾病密切相關(guān)，但由于炎癥性疾病發(fā)病機(jī)制復(fù)雜且影響因素較多，而許多l(xiāng)ncRNA的功能尚不明確，因此lncRNA與炎癥性疾病關(guān)系的研究空間仍然很大。炎癥性疾病中特異性表達(dá)的lncRNA可通過調(diào)控靶基因表達(dá)，發(fā)揮促炎或抗炎作用，進(jìn)而參與疾病發(fā)生、發(fā)展。隨著對(duì)lncRNA功能研究的不斷深入，其有望成為炎癥性疾病診斷的新標(biāo)記物和治療的新靶點(diǎn)。

1 Yan K, Arfat Y, Li D, et al. Structure prediction: new insights into decrypting long noncoding RNAs[J]. Int J Mol Sci, 2016, 17 (1). pii: E132.

2 Pagano A, Castelnuovo M, Tortelli F, et al. New small nuclear RNA gene-like transcriptional units as sources of regulatory transcripts[J]. PLoS Genet, 2007, 3 (2): e1.

3 Wilusz JE, Freier SM, Spector DL. 3’ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA[J]. Cell, 2008, 135 (5): 919-932.

4 Khaitan D, Dinger ME, Mazar J, et al. The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion[J]. Cancer Res, 2011, 71 (11): 3852-3862.

5 Martens JA, Laprade L, Winston F. Intergenic transcription is required to repress theSaccharomycescerevisiaeSER3 gene[J]. Nature, 2004, 429 (6991): 571-574.

6 Hirota K, Miyoshi T, Kugou K, et al. Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs[J]. Nature, 2008, 456 (7218): 130-134.

7 Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs[J]. Cell, 2009, 136 (4): 629-641.

8 Feng J, Bi C, Clark BS, et al. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator[J]. Genes Dev, 2006, 20 (11): 1470-1484.

9 Willingham AT, Orth AP, Batalov S, et al. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT[J]. Science, 2005, 309 (5740): 1570-1573.

10 B?hmdorfer G, Wierzbicki AT. Control of chromatin structure by long noncoding RNA[J]. Trends Cell Biol, 2015, 25 (10): 623-632.

11 Atianand MK, Fitzgerald KA. Long non-coding RNAs and control of gene expression in the immune system[J]. Trends Mol Med, 2014, 20 (11): 623-631.

12 Zhang F, Wu L, Qian J, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus[J]. J Autoimmun, 2016, 75: 96-104.

13 Rapicavoli NA, Qu K, Zhang J, et al. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics[J]. Elife, 2013, 2: e00762.

14 Li Z, Chao TC, Chang KY, et al. The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL[J]. Proc Natl Acad Sci U S A, 2014, 111 (3): 1002-1007.

15 Zhao G, Su Z, Song D, et al. The long noncoding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-κB[J]. FEBS Lett, 2016, 590 (17): 2884-2895.

16 Wang Y, Zhong H, Xie X, et al. Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+T-cell immune responses in tuberculosis infection[J]. Proc Natl Acad Sci U S A, 2015, 112 (29): E3883-E3892.

17 Mirza AH, Berthelsen CH, Seemann SE, et al. Transcriptomic landscape of lncRNAs in inflammatory bowel disease[J]. Genome Med, 2015, 7 (1): 39.

18 Wu F, Huang Y, Dong F, et al. Ulcerative colitis-associated long noncoding RNA, BC012900, regulates intestinal epithelial cell apoptosis[J]. Inflamm Bowel Dis, 2016, 22 (4): 782-795.

19 Chen T, Xue H, Lin R, et al. MiR-34c and PlncRNA1 mediated the function of intestinal epithelial barrier by regulating tight junction proteins in inflammatory bowel disease[J]. Biochem Biophys Res Commun, 2017, 486 (1): 6-13.

20 Chen SW, Wang PY, Liu YC, et al. Effect of long noncoding RNA H19 overexpression on intestinal barrier function and its potential role in the pathogenesis of ulcerative colitis[J]. Inflamm Bowel Dis, 2016, 22 (11): 2582-2592.

21 Chen D, Liu J, Zhao HY, et al. Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn’s disease[J]. World J Gastroenterol, 2016, 22 (19): 4716-4731.

22 Qiao YQ, Huang ML, Xu AT, et al. LncRNA DQ786243 affects Treg related CREB and Foxp3 expression in Crohn’s disease[J]. J Biomed Sci, 2013, 20: 87.

23 Yang L, Long Y, Li C, et al. Genome-wide analysis of long noncoding RNA profile in human gastric epithelial cell response toHelicobacterpylori[J]. Jpn J Infect Dis, 2015, 68 (1): 63-66.

24 Sherrill JD, Kiran KC, Blanchard C, et al. Analysis and expansion of the eosinophilic esophagitis transcriptome by RNA sequencing[J]. Genes Immun, 2014, 15 (6): 361-369.

25 Sookoian S, Rohr C, Salatino A, et al. Genetic variation in long noncoding RNAs and the risk of nonalcoholic fatty liver disease[J]. Oncotarget, 2017, 8 (14): 22917-22926.

26 Wu G, Cai J, Han Y, et al. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity[J]. Circulation, 2014, 130 (17): 1452-1465.

27 Gu S, Li G, Zhang X, et al. Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension[J]. Mol Med Rep, 2015, 11 (4): 2631-2643.

28 Sun C, Xue L, Zhu Z, et al. Insights from lncRNAs profiling of MIN6 beta cells undergoing inflammation[J]. Mediators Inflamm, 2016, 2016: 9275106.

29 Kaur S, Mirza AH, Brorsson CA, et al; Hvidoere International Study Group. The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus[J]. Mol Cell Endocrinol, 2016, 419: 83-91.

30 Yang KY, Chen DL. Shikonin inhibits inflammatory response in rheumatoid arthritis synovial fibroblasts via lncRNA-NR024118[J]. Evid Based Complement Alternat Med, 2015, 2015: 631737.

31 Li X, Chai W, Zhang G, et al. Down-regulation of lncRNA-AK001085 and its influences on the diagnosis of ankylosing spondylitis[J]. Med Sci Monit, 2017, 23: 11-16.

32 Zhou Q, Huang XR, Yu J, et al. Long noncoding RNA Arid2-IR is a novel therapeutic target for renal inflammation[J]. Mol Ther, 2015, 23 (6): 1034-1043.

33 Lin J, Zhang X, Xue C, et al. The long noncoding RNA landscape in hypoxic and inflammatory renal epithelial injury[J]. Am J Physiol Renal Physiol, 2015, 309 (11): F901-F913.

34 Li X, Zeng L, Cao C, et al. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy[J]. Exp Cell Res, 2017, 350 (2): 327-335.

35 Wang L, Wu F, Song Y, et al. Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients[J]. Cell Death Dis, 2016, 7 (8): e2327.

36 Keenan CR, Schuliga MJ, Stewart AG. Pro-inflammatory mediators increase levels of the noncoding RNA GAS5 in airway smooth muscle and epithelial cells[J]. Can J Physiol Pharmacol, 2015, 93 (3): 203-206.

37 Wang W, Gao Z, Wang H, et al. Transcriptome analysis reveals distinct gene expression profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps[J]. Sci Rep, 2016, 6: 26604.

(2017-04-05收稿；2017-05-02修回)

AdvancesinStudyonRelationshipBetweenLncRNAandInflammatoryDiseases

PEIXinyu,CHENZonghao,ZHOUYu.

DepartmentofGastroenterology,AffiliatedHospitalofGuangdongMedicalUniversity,Zhanjiang,GuangdongProvince(524001)

10.3969/j.issn.1008-7125.2017.09.012

國家自然科學(xué)基金面上項(xiàng)目(81570498)

#本文通信作者，Email: ahdg2005@126.com