MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triple-negative breast cancer by directly targeting SETBP1.
MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triple-negative breast cancer by directly targeting SETBP1.
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DOI：
10.1038/bjc.2017.150
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发表时间：
2017-06-27
影响因子：
8.8
通讯作者：
Li JJ
中科院分区：
文献类型：
--
作者：
Chen LL;Zhang ZJ;Yi ZB;Li JJ
三阴性乳腺癌（TNBC）占全球女性所有乳腺癌的15-20%。这种亚型通常具有早期和高复发率，导致生存率低，部分原因是缺乏靶向治疗。迄今为止，TNBC进展的详细分子机制尚不清楚。鉴于microRNAs（miRNAs）在癌症转移中的关键作用，我们的目的是分析转移相关的miRNAs（miR-211- 5 p）在TNBC中的表达和功能。进行miRNA阵列分析以搜索TNBC中的转移相关miRNA。通过实时PCR评估TNBC患者的肿瘤组织、邻近非肿瘤乳腺组织和细胞系中的miR-211- 5 p表达。用免疫印迹、免疫组化和原位杂交分析蛋白表达水平。采用荧光素酶报告基因测定来验证miR-211- 5 p的靶标。在体外和体内研究了miR-211- 5 p对TNBC进展的影响。miR-211- 5 p在TNBC中显著下调，并且其表达水平与TNBC中的总存活率相关。miR-211- 5 p的表达在体外和体内抑制TNBC细胞的增殖、侵袭、迁移和转移。此外，SETBP 1被鉴定为miR-211- 5 p的靶点。通过功能获得和功能丧失研究，SETBP 1显示出在体外显著影响集落和细胞数量。增强miR-211- 5 p表达可显著抑制SETBP 1的表达，恢复SETBP 1表达可逆转miR-211- 5 p对TNBC细胞增殖和转移的抑制作用。这些发现共同证明了miR-211- 5 p通过靶向SETBP 1在TNBC进展中的肿瘤抑制作用，表明miR-211- 5 p可以作为TNBC的潜在预后生物标志物和治疗靶标。
Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer in women globally. This subtype often has early and high recurrence rates, resulting in poor survival, partially due to lack of targeted therapies. To date, the detailed molecular mechanisms underlying TNBC progression are unclear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyse the expression and function of a metastasis-associated miRNA named miR-211-5p in TNBC. MiRNA array analysis was performed to search for metastasis-associated miRNAs in TNBC. The miR-211-5p expression in tumour tissues, adjacent non-tumourous breast tissues of TNBC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analysed by western blot, immunohistochemistry and in situ hybridisation. Luciferase reporter assays were employed to validate the target of miR-211-5p. The effect of miR-211-5p on TNBC progression was investigated in vitro and in vivo. MiR-211-5p was significantly downregulated in TNBC, and its expression level was associated with overall survival in TNBC. The expression of miR-211-5p suppressed TNBC cell proliferation, invasion, migration and metastasis in vitro and in vivo. Furthermore, SETBP1 was identified as a target of miR-211-5p. Through gain-of-function and loss-of-function studies, SETBP1 was shown to significantly affect colony and cell number in vitro. Enforced expression of miR-211-5p inhibited the expression of SETBP1 significantly and the restoration of SETBP1 expression reversed the inhibitory effects of miR-211-5p on TNBC cell proliferation and metastasis. These findings collectively demonstrate a tumour suppressor role of miR-211-5p in TNBC progression by targeting SETBP1, suggesting that miR-211-5p could serve as a potential prognostic biomarker and therapeutic target for TNBC.
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影响因子：
9
作者：
Kanaan, Ziad;Roberts, Henry;Galandiuk, Susan
通讯作者：
Galandiuk, Susan
影响因子：
8.8
作者：
Prat, A.;Lluch, A.;Alba, E.
通讯作者：
Alba, E.
影响因子：
30.8
作者：
Michailidou K;Beesley J;Lindstrom S;Canisius S;Dennis J;Lush MJ;Maranian MJ;Bolla MK;Wang Q;Shah M;Perkins BJ;Czene K;Eriksson M;Darabi H;Brand JS;Bojesen SE;Nordestgaard BG;Flyger H;Nielsen SF;Rahman N;Turnbull C;BOCS;Fletcher O;Peto J;Gibson L;dos-Santos-Silva I;Chang-Claude J;Flesch-Janys D;Rudolph A;Eilber U;Behrens S;Nevanlinna H;Muranen TA;Aittomäki K;Blomqvist C;Khan S;Aaltonen K;Ahsan H;Kibriya MG;Whittemore AS;John EM;Malone KE;Gammon MD;Santella RM;Ursin G;Makalic E;Schmidt DF;Casey G;Hunter DJ;Gapstur SM;Gaudet MM;Diver WR;Haiman CA;Schumacher F;Henderson BE;Le Marchand L;Berg CD;Chanock SJ;Figueroa J;Hoover RN;Lambrechts D;Neven P;Wildiers H;van Limbergen E;Schmidt MK;Broeks A;Verhoef S;Cornelissen S;Couch FJ;Olson JE;Hallberg E;Vachon C;Waisfisz Q;Meijers-Heijboer H;Adank MA;van der Luijt RB;Li J;Liu J;Humphreys K;Kang D;Choi JY;Park SK;Yoo KY;Matsuo K;Ito H;Iwata H;Tajima K;Guénel P;Truong T;Mulot C;Sanchez M;Burwinkel B;Marme F;Surowy H;Sohn C;Wu AH;Tseng CC;Van Den Berg D;Stram DO;González-Neira A;Benitez J;Zamora MP;Perez JI;Shu XO;Lu W;Gao YT;Cai H;Cox A;Cross SS;Reed MW;Andrulis IL;Knight JA;Glendon G;Mulligan AM;Sawyer EJ;Tomlinson I;Kerin MJ;Miller N;kConFab Investigators;AOCS Group;Lindblom A;Margolin S;Teo SH;Yip CH;Taib NA;Tan GH;Hooning MJ;Hollestelle A;Martens JW;Collée JM;Blot W;Signorello LB;Cai Q;Hopper JL;Southey MC;Tsimiklis H;Apicella C;Shen CY;Hsiung CN;Wu PE;Hou MF;Kristensen VN;Nord S;Alnaes GI;NBCS;Giles GG;Milne RL;McLean C;Canzian F;Trichopoulos D;Peeters P;Lund E;Sund M;Khaw KT;Gunter MJ;Palli D;Mortensen LM;Dossus L;Huerta JM;Meindl A;Schmutzler RK;Sutter C;Yang R;Muir K;Lophatananon A;Stewart-Brown S;Siriwanarangsan P;Hartman M;Miao H;Chia KS;Chan CW;Fasching PA;Hein A;Beckmann MW;Haeberle L;Brenner H;Dieffenbach AK;Arndt V;Stegmaier C;Ashworth A;Orr N;Schoemaker MJ;Swerdlow AJ;Brinton L;Garcia-Closas M;Zheng W;Halverson SL;Shrubsole M;Long J;Goldberg MS;Labrèche F;Dumont M;Winqvist R;Pylkäs K;Jukkola-Vuorinen A;Grip M;Brauch H;Hamann U;Brüning T;GENICA Network;Radice P;Peterlongo P;Manoukian S;Bernard L;Bogdanova NV;Dörk T;Mannermaa A;Kataja V;Kosma VM;Hartikainen JM;Devilee P;Tollenaar RA;Seynaeve C;Van Asperen CJ;Jakubowska A;Lubinski J;Jaworska K;Huzarski T;Sangrajrang S;Gaborieau V;Brennan P;McKay J;Slager S;Toland AE;Ambrosone CB;Yannoukakos D;Kabisch M;Torres D;Neuhausen SL;Anton-Culver H;Luccarini C;Baynes C;Ahmed S;Healey CS;Tessier DC;Vincent D;Bacot F;Pita G;Alonso MR;Álvarez N;Herrero D;Simard J;Pharoah PP;Kraft P;Dunning AM;Chenevix-Trench G;Hall P;Easton DF
通讯作者：
Easton DF
影响因子：
3.7
作者：
Kozubek J;Ma Z;Fleming E;Duggan T;Wu R;Shin DG;Dadras SS
通讯作者：
Dadras SS
DOI：
10.1186/bcr3127
发表时间：
2012-02-21
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
van Schooneveld E;Wouters MC;Van der Auwera I;Peeters DJ;Wildiers H;Van Dam PA;Vergote I;Vermeulen PB;Dirix LY;Van Laere SJ
通讯作者：
Van Laere SJ