PMID- 31921620 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 9 DP - 2019 TI - Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer. PG - 1325 LID - 10.3389/fonc.2019.01325 [doi] LID - 1325 AB - Background: Triple-negative breast cancer (TNBC) was characterized by breast cancers that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor (HER)-2 genes. TNBC patients are associated with a shorter median time to relapse and death for the lack of available treatment targets. Long non-coding RNAs (LncRNAs) have been reported to play an important role in the development of TNBC. We identified a novel breast-specific long non-coding RNA LINC00993, but less was known about its expression pattern and functional role in TNBC. Methods: LINC00993 RNA expression was detected across different types of clinical breast cancer samples by using qRT-PCR. Bioinformatic methods "guilt by association" and gene set enrichment analysis (GSEA) were used to predict LINC00993 functions. Subcellular localization of LINC00993 in cells was detected by RNA fluorescence in situ hybridization (FISH). Effect of LINC00993 on cell growth was measured by plate colony formation assays, typical growth curve, and an in vivo tumor model. Cell cycle analysis was done by flow cytometry analysis. Key cell cycle regulators were detected by Western blot. Results: LINC00993 was largely downregulated in TNBC, and higher expression indicated better outcome. LINC00993 located mainly in the nucleus. LINC00993 suppressed TNBC growth both in vitro and in vivo. LINC00993 was predicted to be involved in cell cycle pathways by using "guilt by association" and GSEA methods. Key cell cycle regulators like p16(INK4A), p14(ARF), p53, and p21 were affected by LINC00993 overexpression. Conclusions: A new breast-specific lincRNA LINC00993 was identified with a tumor-suppressive feature and with prognostic value. This is the first research on LINC00993 function. Our results suggest that controlling LINC00993 level may be beneficial for breast cancer treatment. CI - Copyright (c) 2019 Guo, Jian, Tao, Chen, Yu and Liu. FAU - Guo, Shipeng AU - Guo S AD - Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Jian, Lei AU - Jian L AD - Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Tao, Kai AU - Tao K AD - Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Chen, Chen AU - Chen C AD - Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Yu, Haochen AU - Yu H AD - Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Liu, Shengchun AU - Liu S AD - Department of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20191217 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC6928780 OTO - NOTNLM OT - LINC00993 OT - LncRNA OT - TNBC OT - cell cycle OT - guilt by association EDAT- 2020/01/11 06:00 MHDA- 2020/01/11 06:01 PMCR- 2019/01/01 CRDT- 2020/01/11 06:00 PHST- 2019/07/11 00:00 [received] PHST- 2019/11/13 00:00 [accepted] PHST- 2020/01/11 06:00 [entrez] PHST- 2020/01/11 06:00 [pubmed] PHST- 2020/01/11 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2019.01325 [doi] PST - epublish SO - Front Oncol. 2019 Dec 17;9:1325. doi: 10.3389/fonc.2019.01325. eCollection 2019.