Tumor suppressive function of mir-205 in breast cancer is linked to HMGB3 regulation.
Tumor suppressive function of mir-205 in breast cancer is linked to HMGB3 regulation.
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DOI：
10.1371/journal.pone.0076402
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Schmittgen TD
中科院分区：
文献类型：
--
作者：
Elgamal OA;Park JK;Gusev Y;Azevedo-Pouly AC;Jiang J;Roopra A;Schmittgen TD
确定失调的microRNAs（miRNAs）的靶点将增强我们对miRNAs表达改变如何导致乳腺癌恶性表型的理解。与正常样上皮细胞系MCF 10A相比，miR-205在四种乳腺癌细胞系中的表达降低，并且与邻近的良性乳腺组织相比，miR-205在肿瘤和转移组织中的表达降低。在高迁移率族蛋白3基因HMGB 3的3'非翻译区中鉴定了miR-205的两个预测结合位点。双荧光素酶报告基因分析和Western印迹均证实miR-205与HMGB 3结合并调节HMGB 3。为了进一步探索HMGB 3的miR-205靶向，在用前体miR-205寡核苷酸或HMGB 3小干扰RNA（siRNA）瞬时转染的MDA-MB-231和BT549细胞中进行WST-1增殖和体外侵袭测定。两种治疗都减少了癌细胞的增殖和侵袭。HMGB 3的mRNA和蛋白水平在肿瘤中高于邻近的良性标本，并且HMGB 3 mRNA的表达与患者生存率之间存在间接相关性。用5-Aza/TSA处理乳腺癌细胞使miR-205去阻遏，并减少HMGB 3 mRNA，而敲低转录阻遏物NRSF/REST，减少miR-205并增加HMGB 3。总之，miR-205对HMGB 3的调节降低了乳腺癌细胞的增殖和侵袭。我们的研究结果表明，调节miR-205和/或靶向HMGB 3是晚期乳腺癌的潜在治疗方法。
Identifying targets of dysregulated microRNAs (miRNAs) will enhance our understanding of how altered miRNA expression contributes to the malignant phenotype of breast cancer. The expression of miR-205 was reduced in four breast cancer cell lines compared to the normal-like epithelial cell line MCF10A and in tumor and metastatic tissues compared to adjacent benign breast tissue. Two predicted binding sites for miR-205 were identified in the 3’ untranslated region of the high mobility group box 3 gene, HMGB3. Both dual-luciferase reporter assay and Western blotting confirmed that miR-205 binds to and regulates HMGB3. To further explore miR-205 targeting of HMGB3, WST-1 proliferation and in vitro invasion assays were performed in MDA-MB-231 and BT549 cells transiently transfected with precursor miR-205 oligonucleotide or HMGB3 small interfering RNA (siRNA). Both treatments reduced the proliferation and invasion of the cancer cells. The mRNA and protein levels of HMGB3 were higher in the tumor compared to adjacent benign specimens and there was an indirect correlation between the expression of HMGB3 mRNA and patient survival. Treatment of breast cancer cells with 5-Aza/TSA derepressed miR-205 and reduced HMGB3 mRNA while knockdown of the transcriptional repressor NRSF/REST, reduced miR-205 and increased HMGB3. In conclusion, regulation of HMGB3 by miR-205 reduced both proliferation and invasion of breast cancer cells. Our findings suggest that modulating miR-205 and/or targeting HMGB3 are potential therapies for advanced breast cancer.
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影响因子：
--
作者：
Savad, Shahram;Mehdipour, Parvin;Modarressi, Mohammad Hossein
通讯作者：
Modarressi, Mohammad Hossein
正常人组织中microRNA表达谱的表征。
影响因子：
4.4
作者：
Liang, Yu;Ridzon, Dana;Wong, Linda;Chen, Caifu
通讯作者：
Chen, Caifu
影响因子：
6.4
作者：
Chung TK;Cheung TH;Huen NY;Wong KW;Lo KW;Yim SF;Siu NS;Wong YM;Tsang PT;Pang MW;Yu MY;To KF;Mok SC;Wang VW;Li C;Cheung AY;Doran G;Birrer MJ;Smith DI;Wong YF
通讯作者：
Wong YF
影响因子：
4.1
作者：
Greene SB;Herschkowitz JI;Rosen JM
通讯作者：
Rosen JM
影响因子：
8
作者：
Hulf, T.;Sibbritt, T.;Clark, S. J.
通讯作者：
Clark, S. J.