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LPCAT1受FOXA1转录调控,以促进乳腺癌进展和对紫杉醇的耐药性。

LPCAT1 is transcriptionally regulated by FOXA1 to promote breast cancer progression and paclitaxel resistance.

作者信息

Zhang Huayi, Zheng Yaqin

机构信息

Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.

Department of Radiation Oncology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.

出版信息

Oncol Lett. 2023 Feb 15;25(4):134. doi: 10.3892/ol.2023.13720. eCollection 2023 Apr.

Abstract

Bioinformatics analysis indicates that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and forkhead box A1 (FOXA1) are highly expressed in breast cancer tissues and their expression levels are correlated. Therefore, the aim of the present study was to investigate their involvement in the malignant progression and drug resistance of breast cancer. The clinical significance of LPCAT1 was analyzed using The Cancer Genome Atlas data. The enrichment of LPCAT1 in breast cancer cells was determined and the effects of LPCAT1 knockdown on cell proliferation, colony formation, migration, invasion and paclitaxel (PTX) resistance were evaluated. The association between LPCAT1 and FOXA1 was verified using luciferase reporter and chromatin immunoprecipitation assays. Thereafter, the ability of FOXA1 overexpression to regulate LPCAT1 regulation was evaluated. The results revealed that a high LPCAT1 level was associated with poor overall survival in patients with breast cancer. Furthermore, LPCAT1 was found to be highly expressed in breast cancer cells, and its knockdown resulted in suppressed proliferation, colony formation, migration and invasion, and weakened PTX resistance. Furthermore, FOXA1 overexpression attenuated the effects of LPCAT1 knockdown on cells, indicating that FOXA1 transcriptionally regulates LPCAT1. In summary, the present study reveals that LPCAT1 is transcriptionally regulated by FOXA1, which influences breast cancer cell proliferation, metastatic potential and PTX resistance.

摘要

生物信息学分析表明,溶血磷脂酰胆碱酰基转移酶1(LPCAT1)和叉头框A1(FOXA1)在乳腺癌组织中高表达,且它们的表达水平相关。因此,本研究的目的是探讨它们在乳腺癌恶性进展和耐药中的作用。使用癌症基因组图谱数据分析了LPCAT1的临床意义。测定了LPCAT1在乳腺癌细胞中的富集情况,并评估了敲低LPCAT1对细胞增殖、集落形成、迁移、侵袭和紫杉醇(PTX)耐药性的影响。使用荧光素酶报告基因和染色质免疫沉淀试验验证了LPCAT1与FOXA1之间的关联。此后,评估了FOXA1过表达对LPCAT1调控的调节能力。结果显示,LPCAT1水平高与乳腺癌患者的总生存期差相关。此外,发现LPCAT1在乳腺癌细胞中高表达,敲低它会导致细胞增殖、集落形成、迁移和侵袭受到抑制,并削弱PTX耐药性。此外,FOXA1过表达减弱了敲低LPCAT1对细胞的影响,表明FOXA1转录调控LPCAT1。总之,本研究揭示LPCAT1受FOXA1转录调控,这影响乳腺癌细胞增殖、转移潜能和PTX耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e827/9996177/53c5fd17095b/ol-25-04-13720-g00.jpg

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