SiRNA targeting LATS2 promotes proliferation and invasion in breast cancer cells by regulating the Hippo pathway
SiRNA targeting LATS2 promotes proliferation and invasion in breast cancer cells by regulating the Hippo pathway
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靶向 LATS2 的 siRNA 通过调节 Hippo 通路促进乳腺癌细胞的增殖和侵袭
DOI：
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发表时间：
2016
影响因子：
1.4
通讯作者：
Fang, Lin
中科院分区：
文献类型：
--
作者：
Song, Hongming;Song, Jialu;Zhao, Junyong;Fang, Lin
大肿瘤抑制激酶2（LATS 2）是NDR激酶家族的AGC激酶。它是LATS家族的肿瘤抑制因子，在中心体复制、维持有丝分裂保真度和基因组稳定性中起重要作用。已经研究了其可能的肿瘤抑制功能。然而，目前尚不清楚LATS 2是否参与乳腺肿瘤细胞的生长。研究方法：为了研究靶向LATS 2的小干扰RNA（siRNA）对乳腺癌细胞增殖、表达、侵袭、迁移和致瘤能力的影响，将靶向LATS 2的siRNA（LATS 2-siRNA）和阴性对照siRNA转染MDAMB-231和MCF-7细胞。通过定量逆转录聚合酶链反应（qRT-PCR）评估转染细胞中LATS 2的mRNA水平，并通过蛋白质印迹分析评估这些细胞中LATS 2及其下游基因雅普（Yes-associated protein）的蛋白水平。用MTT法、集落形成法、创伤愈合法和transwell小室法检测转染细胞的生长、迁移和侵袭能力。流式细胞术也用于检测内源性LATS 2在乳腺癌细胞中的作用。结果如下：LATS 2-siRNA转染后LATS 2 mRNA表达降低，蛋白表达也有类似趋势，而雅普表达上调。转染LATS 2-siRNA后，乳腺癌细胞增殖和迁移能力增强，细胞凋亡减少，G0/G1期细胞减少。结论：LATS2-siRNA转染乳腺癌MDA-MB-231和MCF-7细胞后，可抑制LATS2的表达，促进细胞增殖、侵袭、迁移，并通过调节Hippo通路破坏细胞周期。因此，靶向LATS 2可能是控制乳腺癌的有效方法。
Large tumor suppressor kinase 2 (LATS2) is an AGC kinase of the NDR family of kinases. It is a tumor suppressor of the LATS family, and plays a significant role in centrosome duplication, maintenance of mitotic fidelity, and genomic stability. It has been investigated for possible tumor suppressing functions. However, it is unclear whether LATS2 is involved in breast tumor cells growth. Methods: In order to estimate the effects of small interfering RNA (siRNA) targeting LATS2 on the proliferation, expression, invasion, migration and tumorigenicity abilities of breast cancer cells, siRNA targeting LATS2 (LATS2-siRNA) and negative control siRNA were transfected into MDAMB-231 and MCF-7 cells. The mRNA levels of LATS2 in the transfected cells were estimated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and the protein levels of LATS2 and its downstream gene YAP (Yes-associated protein) in these cells were evaluated by western blot analysis. The growth, migration and invasion abilities of the transfected cells were measured by MTT, colony formation, wound healing and transwell chamber assay, respectively. Flow cytometry was also used to detect the roles of endogenous LATS2 in breast cancer cells. Results: LATS2 mRNA expression was reduced after transfection with LATS2-siRNA, and protein expression had a similar trend, while the expression of YAP was upregulated. Transfection of LATS2-siRNA promotes breast cancer cells proliferation and migration, inhibits cellular apoptosis, meanwhile less cells were arrested at G0/G1 phase. Conclusions: The transfection of LATS2-siRNA into breast cancer MDA-MB-231 and MCF-7 cells suppressed the expression of LATS2 in these cells, and promoted their proliferation, invasion, migration and disrupted the cell cycle by regulating the Hippo pathway. Therefore, targeting LATS2 may be an efficient approach to control breast cancer.
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影响因子：
11.2
作者：
Li W;Wang L;Katoh H;Liu R;Zheng P;Liu Y
通讯作者：
Liu Y
影响因子：
3.5
作者：
T. Ried;Regina Knutzen;R. Steinbeck;H. Blegen;E. Schröck;K. Heselmeyer;S. Du Manoir;G. Auer
通讯作者：
T. Ried;Regina Knutzen;R. Steinbeck;H. Blegen;E. Schröck;K. Heselmeyer;S. Du Manoir;G. Auer
影响因子：
3.7
作者：
Ke, HN;Pei, J;Tao, WF
通讯作者：
Tao, WF
DOI：
--
发表时间：
2012
期刊：
--
影响因子：
--
作者：
Susan V. Lynch;Katherine C. Goldfarb
通讯作者：
Susan V. Lynch;Katherine C. Goldfarb
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia