孫麗娜 趙曉迪 綜述 盧瑗瑗 王 新 審校
LncRNA與胃腸道腫瘤化療耐藥的研究進(jìn)展
孫麗娜 趙曉迪 綜述 盧瑗瑗 王 新 審校
胃腸道腫瘤化療耐藥使得許多患者治療失敗,而其機(jī)制不清。隨著長(zhǎng)鏈非編碼RNA(Long non-coding RNA,LncRNA)被發(fā)現(xiàn)可在轉(zhuǎn)錄、轉(zhuǎn)錄后及表觀遺傳學(xué)等多個(gè)方面調(diào)控機(jī)體的病理生理過程,許多研究發(fā)現(xiàn)LncRNA與胃腸道腫瘤耐藥也密切相關(guān)。LncRNA不僅與腫瘤的十大特征有著密切聯(lián)系,并且可通過影響藥物轉(zhuǎn)運(yùn)體,以競(jìng)爭(zhēng)內(nèi)源性RNA的作用方式,影響腫瘤細(xì)胞凋亡和調(diào)節(jié)上皮間質(zhì)轉(zhuǎn)化等過程調(diào)控胃腸道腫瘤耐藥。本文就近年來發(fā)現(xiàn)的與胃腸道腫瘤耐藥相關(guān)的LncRNA及其參與胃腸道耐藥的機(jī)制作一綜述。
LncRNA;胃腸道腫瘤;胃癌;結(jié)直腸癌;耐藥
胃腸道腫瘤包括食管癌、胃癌、結(jié)直腸癌等,在惡性腫瘤中發(fā)病率及死亡率均較高。最新的統(tǒng)計(jì)數(shù)據(jù)表明中國(guó)人群中食管癌、胃癌、結(jié)直腸癌的發(fā)病率和死亡率均居惡性腫瘤的前五位[1]。食管癌低T階段(TM)生存率在50%以上,發(fā)生遠(yuǎn)處轉(zhuǎn)移患者五年生存率只有6%[2];胃癌早期五年生存率患者約為70%~95%,而遠(yuǎn)處轉(zhuǎn)移患者五年生存率僅為20%~30%[3];早期結(jié)腸癌和直腸癌的五年生存率分別為91.1%、88.2%,發(fā)生遠(yuǎn)處轉(zhuǎn)移其五年生存率只有13.3%、14%[4]。
目前手術(shù)切除是胃腸道腫瘤的主要治療措施,但是發(fā)生轉(zhuǎn)移患者手術(shù)效果差。雖然以氟尿嘧啶、順鉑、紫杉醇、奧沙利鉑等藥物組成的化療方案在提高轉(zhuǎn)移性胃腸道腫瘤患者的生存期方面發(fā)揮了積極作用,但是腫瘤化療藥物耐藥的出現(xiàn)使得患者化療失敗,并且進(jìn)一步發(fā)生腫瘤遠(yuǎn)處轉(zhuǎn)移、復(fù)發(fā),使得患者生活質(zhì)量下降,生存期縮短。目前研究發(fā)現(xiàn)腫瘤耐藥的發(fā)生涉及多種機(jī)制,比如影響藥物轉(zhuǎn)運(yùn)體系、DNA損傷修復(fù)、逃脫細(xì)胞死亡等[5],但是這些機(jī)制的揭示仍然不能有效地解決臨床耐藥問題。隨著長(zhǎng)鏈非編碼RNA(Long noncoding RNA,LncRNA)被發(fā)現(xiàn)不再是轉(zhuǎn)錄“噪音”,越來越多的研究也發(fā)現(xiàn)LncRNA在胃腸道腫瘤化療耐藥中發(fā)揮了重要作用,其通過與核酸或者蛋白相互作用,以序列特異及結(jié)構(gòu)特異的方式在多個(gè)水平參與調(diào)控基因表達(dá)[6]。本文就近年來LncRNA與胃腸道腫瘤化療耐藥的相關(guān)研究做一綜述,為胃腸道腫瘤化療耐藥后續(xù)研究的開展提供參考。
LncRNA是指長(zhǎng)度在200 nt以上且不具有蛋白編碼功能的轉(zhuǎn)錄本,可通過兩種方式產(chǎn)生:蛋白編碼基因序列蛻變成非編碼基因,或者隨轉(zhuǎn)座因子序列的插入而產(chǎn)生[6]。LncRNA大多在核內(nèi)由RNA聚合酶Ⅱ轉(zhuǎn)錄,轉(zhuǎn)錄完成后,同mRNA一起,一些LncRNA被釋放入胞漿,同時(shí)大多數(shù)轉(zhuǎn)錄本仍然留在核內(nèi),最后LncRNA形成穩(wěn)定的三維立體結(jié)構(gòu)發(fā)揮功能。目前的觀點(diǎn)認(rèn)為,可根據(jù)LncRNA基因組的起源及與蛋白編碼基因的聯(lián)系,將其分為7類:正義LncRNA、反義LncRNA、雙向LncRNA、內(nèi)含子LncRNA、基因間LncRNA、增強(qiáng)子RNA以及環(huán)狀RNA[7]。研究發(fā)現(xiàn)LncRNA的序列保守性差于蛋白編碼基因和microRNA,但優(yōu)于內(nèi)含子和基因間區(qū),其與DNA、RNA及蛋白相互作用的二級(jí)結(jié)構(gòu)的保守性優(yōu)于一級(jí)結(jié)構(gòu),二級(jí)結(jié)構(gòu)的保守性更加決定了LncRNA功能的重要性。此外,研究發(fā)現(xiàn)雖然LncRNA的數(shù)量比mRNA少,但是LncRNA的表達(dá)更具有細(xì)胞特異性。
目前認(rèn)為,LncRNA主要通過以下方式調(diào)控細(xì)胞的生命活動(dòng):(1)轉(zhuǎn)錄水平:LncRNA的表達(dá)水平低,與其臨近基因表達(dá)量相似。與調(diào)節(jié)染色體的蛋白不同,LncRNA發(fā)揮作用不必入核,多以順式調(diào)節(jié)方式發(fā)揮作用。例如酵母SER3基因的表達(dá)受到LncRNA SRG1的調(diào)控,SRG1的3′端存在SER3基因啟動(dòng)子的調(diào)控序列,SRG1成熟后可阻止SER3基因的抑制作用[8]。由于LncRNA可以來源于增強(qiáng)子,故其也有增強(qiáng)子樣的作用;(2)轉(zhuǎn)錄后水平:LncRNA也可在胞漿參與調(diào)節(jié)mRNA。研究證明LncRNA TINCR對(duì)表皮的分化調(diào)控至關(guān)重要,其與STAU1相互作用形成復(fù)合物,維持mRNA的穩(wěn)定性[7];(3)表觀遺傳學(xué)調(diào)控:LncRNA H19和Xist分別參與兩個(gè)重要的表觀遺傳學(xué)基因沉默現(xiàn)象:基因印記及X染色體失活。目前認(rèn)為,LncRNA參與表觀遺傳學(xué)調(diào)控的機(jī)制可能是一種選擇性應(yīng)激反應(yīng),以加強(qiáng)哺乳動(dòng)物基因印記的演進(jìn)[8];(4)信號(hào)分子組裝平臺(tái):LncRNA也被認(rèn)為在多種生物學(xué)信號(hào)事件中為信號(hào)分子的組裝提供了一個(gè)平臺(tái),并且由其精確控制,對(duì)于信號(hào)分子的動(dòng)力學(xué)修飾及相互作用至關(guān)重要[9];(5)定位功能:LncRNA可作為地址編碼的重要成分,使得蛋白復(fù)合物、基因以及染色體被轉(zhuǎn)運(yùn)到正確的位置發(fā)揮其活化或滅活效應(yīng)[6]。
隨著LncRNA研究的深入,發(fā)現(xiàn)其在腫瘤耐藥中發(fā)揮了重大作用。LncRNA與胃腸道腫瘤化療耐藥相關(guān)性的研究如表1所示。研究者們通過高通量篩選的方式獲得與耐藥相關(guān)的LncRNA,并進(jìn)一步進(jìn)行相關(guān)機(jī)制的研究[11-16]。在胃腸道腫瘤中,LncRNA和胃癌及結(jié)直腸癌耐藥的研究較多,對(duì)胃癌的研究多集中在多藥耐藥(Multidrug-resistance,MDR)方面,尤其是阿霉素、順鉑及氟尿嘧啶的耐藥。文獻(xiàn)報(bào)道LncRNA影響耐藥的機(jī)制包括:調(diào)節(jié)DNA損傷和細(xì)胞周期、影響藥物轉(zhuǎn)運(yùn)體系、干擾藥物代謝、影響腫瘤細(xì)胞凋亡以及調(diào)節(jié)上皮間質(zhì)轉(zhuǎn)化(Epithelial-mesenchymal transition,EMT)等[9],LncRNA對(duì)胃腸道腫瘤耐藥影響的機(jī)制既有與上述機(jī)制的相似之處也有其獨(dú)特的方面。
ATP結(jié)合盒超家族成員(ATP-binding cassette,ABC)是影響化療藥物敏感性的重要藥物轉(zhuǎn)運(yùn)體,其對(duì)MDR的影響尤其突出[10]。在胃腸道腫瘤中,LncRNA可通過調(diào)節(jié)ABC超家族蛋白的表達(dá)調(diào)控腫瘤化療耐藥。研究發(fā)現(xiàn)LncRNA ANRIL在順鉑和5-氟尿嘧啶耐藥的胃癌組織及細(xì)胞中均表達(dá)上調(diào),抑制ANRIL可逆轉(zhuǎn)順鉑和5-氟尿嘧啶的耐藥,其作用是通過減少多藥耐藥相關(guān)蛋白MDR1及MRP1的表達(dá)而實(shí)現(xiàn),并且回歸分析發(fā)現(xiàn)ANRIL的表達(dá)與MDR相關(guān)蛋白的表達(dá)呈正相關(guān)[11];LncRNA PVT1與順鉑耐藥的發(fā)生有關(guān),抑制PVT1表達(dá)可逆轉(zhuǎn)胃癌細(xì)胞對(duì)順鉑耐藥,PVT1介導(dǎo)順鉑耐藥的發(fā)生可能是通過調(diào)節(jié)mTOR/HIF-1/P-gp信號(hào)通路以及MRP1實(shí)現(xiàn)[12];LncRNA MRUL在胃癌中是一種MDR相關(guān)LncRNA,MRUL通過促進(jìn)細(xì)胞膜P-糖蛋白(P-gp)的表達(dá)導(dǎo)致相關(guān)化療藥物外排增多、攝入減少?gòu)亩龠M(jìn)MDR形成,抑制MRUL可提高P-gp相關(guān)化療藥物的化療敏感性,研究還發(fā)現(xiàn)MRUL在調(diào)節(jié)P-gp表達(dá)方面可發(fā)揮增強(qiáng)子樣的作用[13-14]。在結(jié)直腸癌中,LncRNA CCAL能夠誘導(dǎo)以5-氟尿嘧啶為基礎(chǔ)的化療方案發(fā)生MDR,其作用是通過抑制AP-2α活性而活化Wnt/β-catenin信號(hào)通路,從而上調(diào)MDR1/P-gp表達(dá)[15]。
表1 胃腸道腫瘤耐藥相關(guān)LncRNA研究
Note:MDR.Multidrug-resistantance;GC.Gastric cancer;CRC.Colorectal cancer;ESCC.Esophageal squamous cell carcinoma.
ceRNA是通過競(jìng)爭(zhēng)性結(jié)合microRNA而相互調(diào)控的轉(zhuǎn)錄本,包括microRNA、LncRNA、偽RNA以及循環(huán)RNA[17]。近期的研究也發(fā)現(xiàn)ceRNA的相互作用參與調(diào)控了腫瘤的惡性表型[23]。研究發(fā)現(xiàn)LncRNA UCA1在胃癌耐藥細(xì)胞中高表達(dá),UCA1可競(jìng)爭(zhēng)性結(jié)合let-7,降低let-7對(duì)耐藥相關(guān)基因HMGA2的抑制,從而使得HMGA2表達(dá)升高,腫瘤細(xì)胞凋亡減少,最終形成胃癌MDR[18];UCA1也可通過競(jìng)爭(zhēng)性結(jié)合miR-27b而調(diào)控胃癌多藥耐藥[19]。而UCA1在結(jié)直腸癌中上調(diào)可通過競(jìng)爭(zhēng)性結(jié)合miR-204-5p以調(diào)控miR-204-5p靶基因CREB1/BCL2/RAB22A而介導(dǎo)MDR[20]。此外,LncRNA H19通過競(jìng)爭(zhēng)性結(jié)合miR-138和miR-200a抑制其靶基因Vimentin、ZEB1及ZEB2的表達(dá),從而調(diào)控結(jié)直腸癌對(duì)氨甲喋呤的敏感性[21];Linc00152可競(jìng)爭(zhēng)性結(jié)合miR-193a-3p并進(jìn)一步調(diào)控ERBB4/Akt信號(hào)軸從而介導(dǎo)結(jié)腸癌奧沙利鉑化療的敏感性[22]。
由于一些腫瘤化療藥物是通過誘導(dǎo)凋亡而抑制腫瘤細(xì)胞的生長(zhǎng),所以凋亡調(diào)節(jié)失控也可引起耐藥的發(fā)生[23]。研究發(fā)現(xiàn)LncRNA UCA1通過影響凋亡通路調(diào)節(jié)胃癌阿霉素化療耐藥,沉默UCA1的表達(dá)可通過上調(diào)PARP蛋白表達(dá)、抑制抗凋亡蛋白Bcl-2表達(dá)而促進(jìn)阿霉素誘導(dǎo)的胃癌細(xì)胞凋亡[24]。在結(jié)直腸癌中,LncRNA CUDR能夠通過抑制藥物誘導(dǎo)的凋亡而誘導(dǎo)阿霉素耐藥,其對(duì)Caspase-3依賴的凋亡抑制發(fā)揮了主要作用[25]。
當(dāng)細(xì)胞發(fā)生EMT時(shí),失去細(xì)胞極性及細(xì)胞間黏附作用,有助于耐藥的發(fā)生[26];近年來隨著腫瘤干細(xì)胞的深入研究,發(fā)現(xiàn)EMT與腫瘤干細(xì)胞的生物學(xué)表型密切相關(guān),而腫瘤干細(xì)胞被認(rèn)為是對(duì)藥物高度耐藥的一群細(xì)胞[27]。研究發(fā)現(xiàn)過表達(dá)LncRNA LEIGC可抑制胃癌生長(zhǎng)和細(xì)胞增殖,提高胃癌細(xì)胞對(duì)5-氟尿嘧啶化療的敏感性,其作用是通過抑制EMT過程發(fā)揮作用[15]。在結(jié)直腸癌中,下調(diào)LncRNA HOTAIR后LoVo細(xì)胞對(duì)5-氟尿嘧啶的耐藥性下降,其作用機(jī)制為上調(diào)E-cadherin且下調(diào)Vimentin的表達(dá)[32]。LncRNA是否通過EMT參與胃腸道腫瘤干細(xì)胞化療耐藥還有待進(jìn)一步研究。
雖然以氟尿嘧啶為主的化療方案在延長(zhǎng)胃腸道腫瘤患者的生存期方面發(fā)揮了積極的作用,但是其逐漸出現(xiàn)的耐藥使得許多患者化療失敗,而化療耐藥的原因仍然不明。目前的一些研究揭示了LncRNA可能通過多種途徑參與胃腸道腫瘤耐藥的形成,但是LncRNA與胃腸道腫瘤耐藥的研究仍然存在著一些問題及諸多挑戰(zhàn):(1)新LncRNA的確立需要進(jìn)一步確定其是否具有蛋白編碼功能,因?yàn)橐恍┍环衷诜蔷幋a分子的LncRNA具有編碼的功能;(2)雖然LncRNA具有明顯的細(xì)胞特異性,而且序列保守性也優(yōu)于內(nèi)含子和基因間區(qū),但是因序列保守性差于蛋白編碼基因和microRNA,故其臨床轉(zhuǎn)化研究進(jìn)展困難,在細(xì)胞及動(dòng)物模型中驗(yàn)證成功的LncRNA不一定能轉(zhuǎn)化到臨床;(3)在對(duì)LncRNA的研究中,功能獲得和缺失實(shí)驗(yàn)所使用的慢病毒工具LncRNA序列為非特異插入,但是LncRNA位置對(duì)功能的影響較大,故研究假陽性較多;(4)LncRNA與胃腸道腫瘤耐藥關(guān)系的研究所使用的研究材料多為永生化的細(xì)胞及誘導(dǎo)耐藥的細(xì)胞系,并未在臨床耐藥前后或耐藥與敏感病人的標(biāo)本中進(jìn)行檢測(cè),不能很好地支持臨床應(yīng)用研究的開展;(5)雖然與胃腸道腫瘤耐藥的LncRNA被發(fā)現(xiàn)得越來越多,但是其確切的機(jī)制研究仍處于初級(jí)階段,LncRNA能否作為靶向治療逆轉(zhuǎn)胃腸道腫瘤耐藥仍然面臨重大挑戰(zhàn)。盡管如此,隨著LncRNA相關(guān)研究的深入以及研究方法的完善,LncRNA與腫瘤耐藥的關(guān)系將逐漸被闡明,其臨床應(yīng)用價(jià)值也將逐步得到檢驗(yàn),有望為解決胃腸道腫瘤患者的化療耐藥問題提供新的可能。
1 Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
2 Saddoughi SA,Reinersman JM,Zhukov YO,et al.Survival after surgical resection of stage IV esophageal cancer[J].Ann Thorac Surg,2017,103(1):261-266.
3 Wohrer SS,Raderer M,Hejna M.Palliative chemotherapy for advanced gastric cancer[J].Ann Oncol,2004,15(11):1585-1595.
4 Siegel RL,Miller KD,F(xiàn)edewa SA,et al.Colorectal cancer statistics,2017[J].CA Cancer J Clin,2017,67(3):177-193.
5 Holohan C,Van Schaeybroeck S,Longley DB,et al.Cancer drug resistance:an evolving paradigm[J].Nat Rev Cancer,2013,13(10):714-726.
6 Wilusz JE,Sunwoo H,Spector DL.Long noncoding RNAs:functional surprises from the RNA world[J].Genes Development,2009,23(13):1494-1504.
7 Ponting CP,Oliver PL,Reik W.Evolution and functions of long noncoding RNAs[J].Cell,2009,136(4):629-641.
8 Beermann J,Piccoli MT,Viereck J,et al.Non-coding RNAs in development and disease:Background,mechanisms,and therapeutic approaches[J].Physiol Rev,2016,96(4):1297-1325.
9 Martens JA,Laprade L,Winston F.Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene[J].Nature,2004,429(6991):571-574.
10 Majidinia M,Yousefi B.Long non-coding RNAs in cancer drug resistance development[J].DNA Repair(Amst),2016,45:25-33.
11 Verstraelen J,Reichl S.Multidrug resistance-associated protein(MRP1,2,4 and 5)expression in human corneal cell culture models and animal corneal tissue[J].Mol Pharm,2014,11(7):2160-2171.
12 Lan WG,Xu DH,Xu C,et al.Silencing of long non-coding RNA ANRIL inhibits the development of multidrug resistance in gastric cancer cells[J].Oncol Rep,2016,36(1):263-270.
13 Zhang XW,Bu P,Liu L,et al.Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance[J].Biochem Biophys Res Commun,2015,462(3):227-232.
14 Wang Y,Zhang D,Wu K,et al.Long noncoding RNA MRUL promotes ABCB1 expression in multidrug-resistant gastric cancer cell sublines[J].Mol Cell Biol,2014,34(17):3182-3193.
15 王穎.長(zhǎng)鏈非編碼RNA DMTF1v4(NR_024549)在胃癌多藥耐藥中的作用及機(jī)制研究[D].陜西:第四軍醫(yī)大學(xué),2012:1-145.
16 Ma Y,Yang Y,Wang F,et al.Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/beta-catenin signalling pathway via suppression of activator protein 2alpha[J].Gut,2016,65(9):1494-1504.
17 Salmena L,Poliseno L,Tay Y,et al.A ceRNA hypothesis:the Rosetta stone of a hidden RNA language?[J].Cell,2011,146(3):353-358.
18 Qi X,Zhang DH,Wu N,et al.ceRNA in cancer:possible functions and clinical implications[J].J Med Genet,2015,52(10):710-718.
19 張哲.長(zhǎng)鏈非編碼RNA分子UCA1介導(dǎo)胃癌多藥耐藥的機(jī)制研究[D].陜西:第四軍醫(yī)大學(xué),2015:1-93.
20 Fang Q,Chen X,Zhi X.Long non-coding RNA(LncRNA)urothelial carcinoma associated 1(UCA1)increases multi-drug resistance of gastric cancer via downregulating miR-27b[J].Med Sci Monit,2016,22:3506-3513.
21 Bian Z,Jin L,Zhang J,et al.LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p[J].Sci Rep,2016,6:23892.
22 Liang WC,F(xiàn)u WM,Wong CW,et al.The LncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer[J].Oncotarget,2015,6(26):22513-22525.
23 Yue B,Cai D,Liu C,et al.Linc00152 functions as a competing endogenous RNA to confer oxaliplatin resistance and holds prognostic values in colon cancer[J].Mol Ther,2016,24(12):2064-2077.
24 Tsuruo T,Naito M,Tomida A,et al.Molecular targeting therapy of cancer:drug resistance,apoptosis and survival signal[J].Cancer Sci,2003,94(1):15-21.
25 Shang C,Guo Y,Zhang J,et al.Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer[J].Cancer Chemother Pharmacol,2016,77(5):1061-1067.
26 Tsang WP,Wong TW,Cheung AH,et al.Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR[J].RNA,2007,13(6):890-898.
27 Radisky DC.Epithelial-mesenchymal transition[J].J Cell Sci,2005,118(Pt 19):4325-4326.
28 Xia H,Hui KM.MicroRNAs involved in regulating epithelial-mesenchymal transition and cancer stem cells as molecular targets for cancer therapeutics[J].Cancer Gene Ther,2012,19(11):723-730.
29 Han Y,Ye J,Wu D,et al.LEIGC long non-coding RNA acts as a tumor suppressor in gastric carcinoma by inhibiting the epithelial-to-mesenchymal transition[J].BMC Cancer,2014,14:932.
30 倪瑤瑤.下調(diào)HOTAIR表達(dá)對(duì)結(jié)直腸癌及其癌干細(xì)胞侵襲、轉(zhuǎn)移和致瘤性的影響[D].南京:東南大學(xué),2015:1-65.
31 Ding J,Li D,Gong M,et al.Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer[J].Onco Targets Ther,2014,7:1625-1630.
32 Lee H,Kim C,Ku JL,et al.A long non-coding RNA snaR contributes to 5-fluorouracil resistance in human colon cancer cells[J].Mol Cells,2014,37(7):540-546.
33 Xiong W,Jiang YX,Ai YQ,et al.Microarray analysis of long non-coding RNA expression profile associated with 5-Fluorouracil-based chemoradiation resistance in colorectal cancer cells[J].Asian Pac J Cancer Prev,2015,16(8):3395-3402.
34 Sun QL,Zhao CP,Wang TY,et al.Expression profile analysis of long non-coding RNA associated with vincristine resistance in colon cancer cells by next-generation sequencing[J].Gene,2015,572(1):79-86.
35 Zhou XL,Wang WW,Zhu WG,et al.High expression of long non-coding RNA AFAP1-AS1 predicts chemoradioresistance and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy[J].Mol Carcinog,2016,55(12):2095-2105.
36 Jiang L,Wang W,Li G,et al.High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma[J].Cancer Chemother Pharmacol,2016,78(2):333-339.
37 Tong YS,Zhou XL,Wang XW,et al.Association of decreased expression of long non-coding RNA LOC285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma[J].J Transl Med,2014,12:233.
ResearchprogressofLncRNAandchemotherapyresistanceingastrointestinalneoplasms
SUNLina,ZHAOXiaodi,LUYuanyuan,WANGXin
State key laboratory of cancer biology,Xijing Hospital of Digestive Disease,F(xiàn)orth Military Medical University,Xi′an 710032,China
Gastrointestinal tumor chemotherapy resistance makes many patients be fail treatment,and its mechanism is unclear.The long-chain non-coding RNA(LncRNA)was found in the transcription,transcription and epigenetic,and other aspects of the regulation of the pathophysiology of the body.Many studies have found that LncRNA is also closely related to gastrointestinal cancer resistance drugs.LncRNA is not only closely related to the ten characteristics of the tumor,but it also regulates gastrointestinal cancer resistance by the impact of drug transporter,competitive endogenous RNA in the way of action,affecting tumor cell apoptosis,and regulating epithelial mesenchymal transition process.This article will review gastrointestinal cancer-related LncRNA and its participation in gastrointestinal resistance mechanism.
LncRNA;Gastrointestinal neoplasms;Gastric cancer;Colorectal cancer;Chemodrug resistance
國(guó)家自然科學(xué)基金(81472701;81572929)
腫瘤生物學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室、第四軍醫(yī)大學(xué)西京消化病醫(yī)院(西安 710032)
孫麗娜,女,(1991-),碩士研究生在讀,從事胃腸道腫瘤的研究。
王新,E-mail:wangx@fmmu.edu.cn
R735
A
10.11904/j.issn.1002-3070.2017.05.012
(收稿:2017-03-04)