丁保鋒
【摘要】 目的:探討miR-577靶向調(diào)控HOXA1對(duì)乳腺癌MDB-MA-231細(xì)胞增殖、侵襲和遷移的影響。方法:將體外培養(yǎng)的MDB-MA-231細(xì)胞分為對(duì)照組(未處理)、miR-NC組(轉(zhuǎn)染miR-577模擬物陰性對(duì)照)、miR-577組(轉(zhuǎn)染miR-577模擬物)、miR-577+pcDNA組(轉(zhuǎn)染miR-577模擬物和pcDNA3.1質(zhì)粒)和miR-577+HOXA1組(轉(zhuǎn)染miR-577模擬物和pcDNA3.1-HOXA1質(zhì)粒),采用實(shí)時(shí)熒光定量PCR測(cè)定MDB-MA-231細(xì)胞中miR-577和HOXA1 mRNA的表達(dá),Western blot測(cè)定HOXA1蛋白表達(dá),熒光素酶報(bào)告基因?qū)嶒?yàn)測(cè)定miR-577和HOXA1的靶向關(guān)系,CCK-8法測(cè)定MDB-MA-231細(xì)胞增殖,流式細(xì)胞儀測(cè)定細(xì)胞周期分布,Transwell小室測(cè)定MDB-MA-231細(xì)胞侵襲和遷移。結(jié)果:與對(duì)照組、miR-NC組相比,miR-577組細(xì)胞中miR-577表達(dá)水平、G0/G1期細(xì)胞百分比升高,HOXA1 mRNA和蛋白表達(dá)水平、48與72 h細(xì)胞增殖活力、S期細(xì)胞百分比、侵襲細(xì)胞數(shù)和遷移細(xì)胞數(shù)均降低,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。與miR-577組、miR-577+pcDNA組相比,miR-577+HOXA1組中HOXA1 mRNA和蛋白表達(dá)水平、48與72 h細(xì)胞增殖活力、S期細(xì)胞百分比、侵襲細(xì)胞數(shù)和遷移細(xì)胞數(shù)均升高,G0/G1期百分比降低,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論:miR-577可通過(guò)靶向HOXA1抑制MDB-MA-231細(xì)胞增殖、侵襲和遷移。
【關(guān)鍵詞】 miR-577 乳腺癌 HOXA1 增殖 侵襲 遷移
Effects of miR-577 Inhibits Proliferation, Migration and Invasion of Breast Cancer MDB-MA-231 Cells by Targeting HOXA1/DING Baofeng. //Medical Innovation of China, 2021, 18(10): 0-018
[Abstract] Objective: To investigate the effects of miR-577 targeting HOXA1 on proliferation, invasion and migration of breast cancer MDB-MA-231 cells. Method: MDB-MA-231 cells cultured in vitro were divided into control group (untreated), miR-NC group (transfected negative control of miR-577 mimics), miR-577 group (transfected miR-577mimics), miR-577+pcDNA group (transfected miR-577 mimics and pcDNA 3.1 plasmids) and miR-577+HOXA1 group (transfected miR-577 mimics and pcDNA3.1-HOXA1 plasmids). The expression of miR-577 and HOXA1 mRNA in MDB-MA-231 cells were detected by real-time fluorescence quantitative PCR, the expression of HOXA1 protein was measured by Western blot, the targeting relationship between miR-577 and HOXA1 was checked by double luciferase reporter gene assay, the proliferation of MDB-MA-231 cells was tested by CCK-8, the cell cycle was examed by flow cytometry, the migration and invasion of MDB-MA-231 cells were detected by Transwell chamber. Result: Compared with the control group and the miR-NC group, the expression level of miR-577 and the percentage of G0/G1 phase cells in the miR-577 group were increased, the expression levels of HOXA1 mRNA and protein, the proliferation activity of cells at 48 and 72 h, the percentage of cells in the S phase, the number of invaded cells and the number of migrated cells were decreased, the differences were statistical significance (P<0.05). Compared with the miR-577 group and the miR-577+pcDNA group, HOXA1 mRNA and protein expression levels, proliferation activity of cells at 48 and 72 h, percentage of cells in S phase, number of invading cells and number of migrating cells in the miR-577+HOXA1 group were all increased, while percentage of cells in G0/G1 phase was decreased, the differences were statistical significance (P<0.05). Conclusion: miR-577 can inhibit proliferation, invasion and migration of MDB-MA-231 cells by targeting HOXA1.
[Key words] miR-577 Breast cancer HOXA1 Proliferation Invasion Migration
First-authors address: The Central Hospital of Jiamusi City, Jiamusi 154002, China
doi:10.3969/j.issn.1674-4985.2021.10.004
微小RNAs(microRNAs,miRNAs)是一類(lèi)廣泛分布于機(jī)體血液、組織和唾液中的內(nèi)源性非編碼RNA,常被作為腫瘤早期診斷和預(yù)后不良的重要指標(biāo),也是腫瘤基因治療的潛在靶分子,其可通過(guò)堿基互補(bǔ)配對(duì)抑制翻譯或降解靶mRNA參與包括乳腺癌在內(nèi)的多種腫瘤的發(fā)生發(fā)展[1]。miR-577是miRNAs中的重要成員,被證實(shí)在肝癌、結(jié)腸癌和膠質(zhì)母細(xì)胞瘤等腫瘤細(xì)胞增殖、侵襲和遷移過(guò)程中發(fā)揮著重要的抑制作用[2-3]。Yin等[4]證實(shí)miR-577在乳腺癌組織中低表達(dá),與腫瘤大小、腫瘤分期和淋巴轉(zhuǎn)移等有關(guān),可通過(guò)靶向Rab25抑制癌細(xì)胞上皮間質(zhì)轉(zhuǎn)化和轉(zhuǎn)移;但miR-577在乳腺癌中的作用及機(jī)制并不完全清晰。同源盒A1(HOXA1)是同源盒(HOX)基因家族成員,被證實(shí)在乳腺癌中異常高表達(dá),通過(guò)調(diào)控癌細(xì)胞增殖、侵襲和遷移等促進(jìn)腫瘤進(jìn)展[5]。有研究指出,miR-577可通過(guò)靶向調(diào)控HOXA1表示抑制肝癌細(xì)胞侵襲和遷移,但其是否可能通過(guò)靶向調(diào)控HOXA1影響乳腺癌的發(fā)生發(fā)展尚不清楚[6]。因此,本研究以乳腺癌MDB-MA-231細(xì)胞為研究對(duì)象,通過(guò)觀察miR-577與HOXA1的靶向關(guān)系,探討miR-577通過(guò)靶向調(diào)控HOXA1對(duì)MDB-MA-231細(xì)胞增殖、侵襲和遷移等影響,以期為miR-577用于乳腺癌的治療靶點(diǎn)提供一定的實(shí)驗(yàn)依據(jù),現(xiàn)報(bào)道如下。
1 材料與方法
1.1 材料與試劑 人乳腺癌MDB-MA-231細(xì)胞株購(gòu)于美國(guó)ATCC,BCA蛋白濃度試劑盒購(gòu)于上海碧云天公司,CCK-8試劑盒購(gòu)于上海威奧生物公司,碘化丙啶購(gòu)于北京索萊寶公司,Lipo2000購(gòu)于美國(guó)Invitrogen公司,DMEM培養(yǎng)基購(gòu)于美國(guó)Gibco公司,兔抗人HOXA1單克隆抗體購(gòu)于美國(guó)Sigma公司,鼠抗人GAPDH單克隆抗體和羊抗鼠/兔IgG二抗購(gòu)于美國(guó)Santa Cruz Biotechnology公司。ECL底物液購(gòu)于美國(guó)Thermo公司,Transwell購(gòu)于美國(guó)BD Biosciences公司,反轉(zhuǎn)錄和qPCR試劑盒購(gòu)于大連寶生物公司,Dual luciferase assays試劑盒購(gòu)于美國(guó)Promega公司。PCR引物由上海生工公司合成。pcDNA3.1-HOXA1過(guò)表達(dá)載體質(zhì)粒由上海北諾生物公司設(shè)計(jì)完成。miR-577模擬物及其陰性對(duì)照購(gòu)于廣州銳博生物公司。
1.2 方法
1.2.1 MDB-MA-231細(xì)胞培養(yǎng)與轉(zhuǎn)染 實(shí)驗(yàn)分組:對(duì)照組(未處理)、miR-NC組(轉(zhuǎn)染miR-577模擬物陰性對(duì)照)、miR-577組(轉(zhuǎn)染miR-577模擬物),miR-577+pcDNA組(轉(zhuǎn)染miR-577模擬物和pcDNA3.1質(zhì)粒)和miR-577+HOXA1組(轉(zhuǎn)染miR-577模擬物和pcDNA3.1-HOXA1質(zhì)粒)。
1.2.2 實(shí)時(shí)熒光定量PCR測(cè)定miR-577和HOXA1 mRNA的表達(dá) 取轉(zhuǎn)染后的MDB-MA-231細(xì)胞于EP管中,應(yīng)用Trizol試劑提取細(xì)胞總RNA。將定量后的RNA作為模板,參照逆轉(zhuǎn)錄試劑盒說(shuō)明書(shū)合成cDNA。取稀釋10倍的cDNA 4 μL作為模板,并與100 μm的上下游引物各0.4 μL、SYBR Green qPCR Master Mix(2×)10 μL和ddH2O 5.2 μL混勻配成20 μL的PCR反應(yīng)體系;并按照94 ℃、6 min,94 ℃、30 s,60 ℃、30 s,
共40個(gè)循環(huán)的反應(yīng)條件行溶解曲線。程序完成后,以U6和GAPDH為內(nèi)參,2-△△Ct法進(jìn)行數(shù)據(jù)分析。miR-577引物序列(F:5-ACCGCGCGCGCGTAGATAAAATATTGG-3,R:5-ATCCAGTGCAGGGTCCGAGG-3),U6引物序列(F:5-CGCTTCGGCAGCACATATAC-3,R:5-AAATATGGAACGCTTCACGA-3),HOXA1引物序列(F:5-TCCTGGAATACCCCATACTTAGCA-3,R:5-GCCGCCGCAACTGTTG-3)和GAPDH引物序列(F:5-TGACTTCAACAGCGACACCCA-3,R:5-CACCCTGTTGCTGTAGCCAAA-3)。
1.2.3 Western blot測(cè)定HOXA1蛋白的表達(dá) 將收集到的MDB-MA-231細(xì)胞以磷酸緩沖液洗滌后,加入預(yù)冷的細(xì)胞裂解液抽取總蛋白。根據(jù)BCA蛋白檢測(cè)試劑盒說(shuō)明書(shū)對(duì)總蛋白的濃度進(jìn)行定量。取50 μg蛋白樣品行12%SDS-PAGE電泳(120 V,
2 h)分離后,轉(zhuǎn)PVDF膜(250 mA,1.5 h)。轉(zhuǎn)入含50 g/L脫脂奶粉的TBST封閉液中室溫作用1 h。將膜轉(zhuǎn)入封閉液稀釋工作濃度分別為1︰500和
1︰1 000的HOXA1抗體和GAPDH抗體,4 ℃下孵育過(guò)夜。再轉(zhuǎn)入封閉液稀釋1︰5 000的二抗常溫孵育2 h。將ECL工作液滴加到PVDF膜上,置于暗室內(nèi)顯影、曝光。采用凝膠成像系統(tǒng)掃描分析HOXA1蛋白的表達(dá)水平。
1.2.4 CCK-8法測(cè)定MDB-MA-231細(xì)胞增殖情
況 采用胰蛋白酶消化收集轉(zhuǎn)染48 h后的各組MDB-MA-231細(xì)胞,以每孔10 000個(gè)細(xì)胞密度接種至96孔細(xì)胞板上,每組設(shè)置5個(gè)平行孔。放入培養(yǎng)箱內(nèi)分別培養(yǎng)24、48、72 h后,每孔加入10 μL CCK-8試劑反應(yīng)4 h后,上機(jī)于450 nm波長(zhǎng)處檢測(cè)各組細(xì)胞的光密度值。重復(fù)檢測(cè)3次。
1.2.5 流式細(xì)胞儀測(cè)定MDB-MA-231細(xì)胞的周期變化 以磷酸緩沖液(預(yù)冷)洗滌收集到的各組MDB-MA-231細(xì)胞后,預(yù)冷的70%乙醇固定細(xì)胞12 h。經(jīng)磷酸緩沖液洗滌后,以碘化丙啶對(duì)細(xì)胞染色30 min,上機(jī)于488 nm處檢測(cè)各組MDB-MA-231細(xì)胞的周期變化。
1.2.6 Transwell小室測(cè)定MDB-MA-231細(xì)胞侵襲遷移情況 將轉(zhuǎn)染48 h后的各組MDB-MA-231細(xì)胞制成濃度為3 000個(gè)/mL的細(xì)胞懸液。取200 μL細(xì)胞液加入以基質(zhì)膠包被或不包被的Transwell小室上室中,另取含胎牛血清的培養(yǎng)液600 μL加入到小室下室中。放入培養(yǎng)箱中培養(yǎng)過(guò)夜。將小室取出,小心擦去上室內(nèi)殘留的細(xì)胞,經(jīng)4%多聚甲醛固定和0.5%結(jié)晶紫后,顯微鏡下隨機(jī)選取5個(gè)視野統(tǒng)計(jì)下室面的細(xì)胞數(shù)量,結(jié)果取均值。
1.2.7 熒光素酶報(bào)告基因?qū)嶒?yàn)測(cè)定miR-577與HOXA1的關(guān)系 應(yīng)用TargetScanHuman軟件預(yù)測(cè)到miR-577與HOXA1的3-UTR存在互補(bǔ)的核苷酸序列。構(gòu)建突變型HOXA1-MUT和野生型HOXA1-WT的HOXA1 3-UTR熒光素酶報(bào)告載體,參照Lipo 2 000說(shuō)明書(shū)行miR-577+HOXA1-MUT(共轉(zhuǎn)染miR-577模擬物和HOXA1-MUT)、miR-577+HOXA1-WT(共轉(zhuǎn)染miR-577模擬物和HOXA1-WT)、miR-NC+HOXA1-MUT(共轉(zhuǎn)染miR-577模擬物陰性對(duì)照和HOXA1-MUT)和miR-NC+HOXA1-WT(共轉(zhuǎn)染miR-577模擬物陰性對(duì)照和HOXA1-WT)四組共轉(zhuǎn)染,培養(yǎng)箱內(nèi)常規(guī)培養(yǎng)48 h后,根據(jù)Dual luciferase assays試劑盒說(shuō)明書(shū)測(cè)定各組細(xì)胞的熒光素酶活性。
1.3 統(tǒng)計(jì)學(xué)處理 采用SPSS 22.0軟件對(duì)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析,計(jì)量資料以(x±s)表示,兩組間比較采用獨(dú)立樣本t檢驗(yàn),組間多重比較采用SNK-q,多組間比較使用單因素方差分析;計(jì)數(shù)資料以率(%)表示,比較采用字2檢驗(yàn)。以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 轉(zhuǎn)染后MDB-MA-231細(xì)胞中miR-577和HOXA1的表達(dá)結(jié)果 與對(duì)照組、miR-NC組相比,miR-577組細(xì)胞中miR-577的表達(dá)水平均顯著升高,而HOXA1 mRNA和蛋白的表達(dá)水平均顯著降低(P<0.05);與miR-577組、miR-577+pcDNA組比較,miR-577+HOXA1組細(xì)胞中miR-577水平差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),而HOXA1 mRNA和蛋白的表達(dá)水平均顯著升高(P<0.05);而miR-NC組與對(duì)照組比較,miR-577組與miR-577+pcDNA組比較,miR-577表達(dá)、HOXA1 mRNA和蛋白表達(dá)水平的差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)圖1、表1。
2.2 miR-577與HOXA1的靶向關(guān)系 經(jīng)TargetScanHuman軟件預(yù)測(cè)發(fā)現(xiàn),miR-577與HOXA1 3 UTR存在互補(bǔ)核苷酸序列,見(jiàn)表2。
miR-NC+HOXA1-WT組熒光素酶活性值為(0.98±0.06),miR-577+HOXA1-WT組熒光素酶活性值為(0.39±0.03),miR-NC+HOXA1-MUT組熒光素酶活性值為(0.96±0.06),miR-577+HOXA1-MUT組熒光素酶活性值為(0.94±0.05)。與miR-NC+HOXA1-WT組相比,miR-577+HOXA1-WT組細(xì)胞的熒光素酶活性顯著降低(P<0.05);而miR-NC+HOXA1-MUT組與miR-577+HOXA1-MUT組細(xì)胞熒光素酶活性比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);四組間比較差異有統(tǒng)計(jì)學(xué)意義(F=92.255,P=0.000)。
2.3 miR-577靶向調(diào)控HOXA1對(duì)MDB-MA-231細(xì)胞增殖的影響 miR-577組與對(duì)照組、miR-NC組相比,miR-577+HOXA1組與miR-577組、miR-577+pcDNA組相比,細(xì)胞在24 h作用時(shí)間下增殖活力差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。在48、72 h
作用時(shí)間下,miR-577組的細(xì)胞增殖活力較對(duì)照組、miR-NC組均明顯減弱(P<0.05),miR-577+HOXA1組較miR-577組、miR-577+pcDNA組均顯著增強(qiáng)(P<0.05);而miR-NC組與對(duì)照組相比,miR-577+pcDNA組與miR-577組相比,細(xì)胞增殖活力差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表3。
2.4 miR-577靶向調(diào)控HOXA1對(duì)MDB-MA-231細(xì)胞周期的影響 miR-577組、miR-577+pcDNA組和miR-577+HOXA1組中G0/G1期細(xì)胞百分比均顯著高于對(duì)照組、miR-NC組,S期細(xì)胞百分比均顯著低于對(duì)照組、miR-NC組(P<0.05),G2/M期細(xì)胞百分比與對(duì)照組、miR-NC組比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);miR-577+HOXA1組中G0/G1期細(xì)胞百分比較miR-577組、miR-577+pcDNA組顯著降低,S期細(xì)胞百分比較miR-577組、miR-577+pcDNA組顯著升高(P<0.05),G2/M期細(xì)胞百分比與miR-577組、miR-577+pcDNA組比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);而對(duì)照組與miR-NC組、miR-577+pcDNA組與miR-577組G0/G1期、S期及G2/M期細(xì)胞百分比比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表4。
2.5 miR-577靶向調(diào)控HOXA1對(duì)MDB-MA-231細(xì)胞侵襲和遷移的影響 與對(duì)照組、miR-NC組相比,而miR-577組侵襲細(xì)胞數(shù)和遷移細(xì)胞數(shù)中均顯著減少(P<0.05);與miR-577組、miR-577+pcDNA組相比,miR-577+HOXA1組中侵襲細(xì)胞數(shù)和遷移細(xì)胞數(shù)顯著增多(P<0.05);而對(duì)照組與miR-NC組相比,miR-577組與miR-577+pcDNA組相比,差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表5。
3 討論
乳腺癌是一種起源于乳腺腺上皮組織的惡性腫瘤,多見(jiàn)于女性;近年來(lái)其發(fā)病率有升高和年輕化的趨勢(shì),嚴(yán)重威脅著女性身體健康[7-9]。深入探討乳腺癌的發(fā)生發(fā)展機(jī)制,尋找新的有效的治療靶點(diǎn)對(duì)治療乳腺癌具有重要意義。近年來(lái),miR-577在腫瘤發(fā)生發(fā)展中的作用逐漸引起關(guān)注。在胃癌的研究中,何銀平等[10]證實(shí),miR-577表達(dá)下調(diào),且與腫瘤TNM分期、淋巴結(jié)轉(zhuǎn)移等有關(guān),上調(diào)其表達(dá)可通過(guò)下調(diào)β-catenin抑制癌細(xì)胞侵襲;Yu等[11]指出,miR-577過(guò)表達(dá)可通過(guò)靶向調(diào)控E2F3誘導(dǎo)癌細(xì)胞阻滯于G1期抑制胃癌細(xì)胞增殖。Wang等[12]在非小細(xì)胞肺癌的研究發(fā)現(xiàn),miR-577表達(dá)下調(diào),上調(diào)其表達(dá)可通過(guò)調(diào)節(jié)Wnt2b介導(dǎo)的Wnt/β-catenin途徑抑制細(xì)胞增殖、侵襲、遷移和上皮間充質(zhì)轉(zhuǎn)化。在甲狀腺乳頭狀癌研究中,miR-577表達(dá)下降,其過(guò)表達(dá)可通過(guò)靶向調(diào)控Sphk2抑制癌細(xì)胞增殖、侵襲和遷移[13]。另外,miR-577在腫瘤發(fā)生發(fā)展中的抑癌作用在肝癌、結(jié)腸癌和膠質(zhì)瘤等中也得以證實(shí)[14-16]。本研究結(jié)果顯示,miR-577過(guò)表達(dá)可抑制乳腺癌MDB-MA-231增殖、侵襲、遷移并誘導(dǎo)細(xì)胞周期阻滯于G0/G1期,這提示,miR-577在乳腺癌發(fā)生發(fā)展過(guò)程中也發(fā)揮著與上述文獻(xiàn)相似的抑癌作用。
HOX基因家族是一類(lèi)與腫瘤發(fā)生發(fā)展關(guān)系密切的轉(zhuǎn)錄調(diào)節(jié)因子,通過(guò)結(jié)合DNA調(diào)控相關(guān)基因表達(dá),在細(xì)胞增殖、侵襲和遷移等過(guò)程中發(fā)揮著重要作用[17-18]。HOXA1是HOX基因家族成員,其異常表達(dá)也往往影響著腫瘤的惡性進(jìn)展。研究顯示,HOXA1在胃癌組織中的蛋白陽(yáng)性表達(dá)率明顯升高,且其高表達(dá)的患者3年生存率明顯低于低表達(dá)患者,其促進(jìn)胃癌發(fā)展進(jìn)程[19];AFAP1-AS1在口腔鱗狀細(xì)胞癌中表達(dá)升高,敲低其表達(dá)可通過(guò)競(jìng)爭(zhēng)性吸附miR-145進(jìn)而抑制HOXA1的表達(dá)降低口腔鱗狀細(xì)胞癌細(xì)胞的增殖、遷移和侵襲能力,AFAP1-AS1/miR-145/HOXA1軸為口腔鱗狀細(xì)胞癌的治療提供了潛在分子靶點(diǎn)[20];miR-100可通過(guò)靶向抑制HOXA1阻礙非細(xì)胞肺癌細(xì)胞的增殖、侵襲和遷移能力,miR-100/HOXA1軸在非細(xì)胞肺癌細(xì)胞中發(fā)揮抑癌基因作用[21];HOXA1在乳腺癌中異常高表達(dá),在腫瘤細(xì)胞增殖、侵襲和遷移過(guò)程中發(fā)揮著重要的促進(jìn)作用,敲低其表達(dá)可抑制乳腺癌的惡性進(jìn)展[22]。猜測(cè)miR-577可能通過(guò)靶向HOXA1調(diào)控細(xì)胞增殖、侵襲和遷移進(jìn)而影響乳腺癌的進(jìn)展。為了探討miR-577抑制乳腺癌進(jìn)展的分子機(jī)制,本研究通過(guò)生物信息學(xué)軟件預(yù)測(cè)到miR-577與HOXA1 3 UTR存在互補(bǔ)核苷酸序列,熒光素酶報(bào)告基因?qū)嶒?yàn)證實(shí),HOXA1是miR-577的一個(gè)潛在靶基因。同時(shí),過(guò)表達(dá)HOXA1后miR-577對(duì)MDB-MA-231細(xì)胞增殖、侵襲和遷移的作用均明顯得到部分逆轉(zhuǎn)。這提示,miR-577可通過(guò)靶向調(diào)控HOXA1抑制MDB-MA-231細(xì)胞增殖、侵襲和遷移。
綜上所述,HOXA1是miR-577的潛在靶基因,miR-577可通過(guò)靶向HOXA1抑制乳腺癌MDB-MA-231細(xì)胞增殖、遷移和侵襲。該結(jié)果可能為miR-577有望成為乳腺癌治療的候選基因提供重要的參考依據(jù)。
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(收稿日期:2020-07-13) (本文編輯:劉蓉艷)