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DSCAM-AS1 调控 G/S 细胞周期转换，是内分泌治疗的 luminal 型乳腺癌患者不良预后的独立预测因子。

DSCAM-AS1 regulates the G /S cell cycle transition and is an independent prognostic factor of poor survival in luminal breast cancer patients treated with endocrine therapy.

机构信息

Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.

出版信息

Cancer Med. 2018 Dec;7(12):6137-6146. doi: 10.1002/cam4.1603. Epub 2018 Nov 14.

DOI:10.1002/cam4.1603
PMID:30430768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6308059/
Abstract

DSCAM-AS1 is one of the few intensively studied lncRNAs with high specific expression in luminal breast cancer. It is directly regulated by estrogen receptor α (ERα) and plays vital roles in tumor proliferation, invasion, and tamoxifen resistance. However, the detailed function of DSCAM-AS1 in tumor progression and its clinical significance remain unclear. We reveal that DSCAM-AS1 regulates cell proliferation and colony formation by inducing the G1/S transition. RNA-seq analysis demonstrated that DSCAM-AS1 participates in crucial biological processes, including DNA replication, the G1/S phase transition, sister chromatid cohesion, chromosome segregation, protein localization to the chromosome and DNA recombination. Most importantly, in the retrospectively registered clinical analysis, high expression of DSCAM-AS1 is a poor prognostic factor in patients with luminal breast cancer treated with endocrine therapy. In conclusion, DSCAM-AS1 is a promising clinical therapeutic target that may prolong survival of luminal breast cancer patients treated with endocrine therapy.

摘要

DSCAM-AS1 是少数几种在腔腺癌中高度特异性表达的长链非编码 RNA 之一。它受雌激素受体 α（ERα）的直接调控，在肿瘤增殖、侵袭和他莫昔芬耐药中发挥重要作用。然而，DSCAM-AS1 在肿瘤进展中的详细功能及其临床意义尚不清楚。我们揭示 DSCAM-AS1 通过诱导 G1/S 期转变来调节细胞增殖和集落形成。RNA-seq 分析表明，DSCAM-AS1 参与了包括 DNA 复制、G1/S 期转换、姐妹染色单体黏合、染色体分离、蛋白定位到染色体和 DNA 重组在内的关键生物学过程。最重要的是，在回顾性注册的临床分析中，DSCAM-AS1 的高表达是接受内分泌治疗的腔腺癌患者的预后不良因素。总之，DSCAM-AS1 是一种很有前途的临床治疗靶点，可能延长接受内分泌治疗的腔腺癌患者的生存时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/ef1d0f67fb64/CAM4-7-6137-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/72b5e295ea60/CAM4-7-6137-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/06446bc4b32d/CAM4-7-6137-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/ef1d0f67fb64/CAM4-7-6137-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/72b5e295ea60/CAM4-7-6137-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/06446bc4b32d/CAM4-7-6137-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/6308059/ef1d0f67fb64/CAM4-7-6137-g003.jpg

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