PMID- 31062358 OWN - NLM STAT- MEDLINE DCOM- 20200609 LR - 20211204 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 12 DP - 2019 Dec TI - Assessment of the expression pattern of mTOR-associated lncRNAs and their genomic variants in the patients with breast cancer. PG - 22044-22056 LID - 10.1002/jcp.28767 [doi] AB - The mechanistic target of rapamycin (mTOR) is a fundamental component of a signaling pathway that is involved in the pathogenesis of breast cancer via different mechanisms. This pathway is functionally linked with a number of small nucleolar RNA host genes (SNHGs). In the present project, we have searched for the expression quantitative trait loci (eQTLs) within SNHGs that are possibly involved in the pathogenesis of breast cancer. Following this in silico step, we have assessed expression levels of mTOR and four SNHGs in malignant and nonmalignant samples obtained from 80 patients with breast cancer. We also genotyped rs4615861 of SNHG3 and rs3087978 of SNHG5 in the peripheral blood of patients. SNHG12 expression was not detected in any of the assessed malignant or nonmalignant tissues. So this gene was excluded from further steps. Expression of mTOR and other three long noncoding RNAs (lncRNAs) were significantly increased in the malignant tissues compared with the nonmalignant tissues. When classifying patients into down-/upregulation categorized based on the transcript levels of each gene in malignant tissue versus nonmalignant tissues, we noticed associations between expression of SNHG1 and stage (p = 0.03), expression of SNHG5 and grade (p = 0.05), as well as between expression of SNHG3 and history of oral contraceptive use (p = 0.04). We also detected higher levels of SNHG3 expression in estrogen receptor/progesterone receptor (ER/PR) negative tumors compared with the ER/PR positive tumors (p = 0.003 and p = 0.01, respectively). Moreover, there was a trend toward higher expression of this lncRNA in HER2-positive tumors compared with the HER2-negative ones (p = 0.07). Combination of transcript levels of all genes could differentiate malignant tissues from nonmalignant tissues with the diagnostic power of 69% (p = 0.0001). The rs3087978 was associated with the expression of mTOR in malignant tissues in a way that TT and TG genotypes were associated with the higher and lower levels of expressions, respectively (p = 0.01). The current study underscores the significance of SNHGs in the pathogenesis of breast cancer. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Taherian-Esfahani, Zahra AU - Taherian-Esfahani Z AD - Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Taheri, Mohammad AU - Taheri M AUID- ORCID: 0000-0001-8381-0591 AD - Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Dashti, Sepideh AU - Dashti S AD - Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Kholghi-Oskooei, Vahid AU - Kholghi-Oskooei V AD - Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Geranpayeh, Lobat AU - Geranpayeh L AD - Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Ghafouri-Fard, Soudeh AU - Ghafouri-Fard S AUID- ORCID: 0000-0002-0223-499X AD - Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190506 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (RNA, Long Noncoding) RN - 0 (long non-coding RNA SNHG5, human) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adult MH - Breast Neoplasms/*genetics/pathology MH - Female MH - Genetic Variation MH - Genotype MH - Humans MH - Middle Aged MH - Quantitative Trait Loci MH - RNA, Long Noncoding/*genetics MH - TOR Serine-Threonine Kinases/*genetics MH - Transcriptome OTO - NOTNLM OT - breast cancer OT - lncRNA OT - mTOR EDAT- 2019/05/08 06:00 MHDA- 2020/06/10 06:00 CRDT- 2019/05/08 06:00 PHST- 2019/03/06 00:00 [received] PHST- 2019/04/13 00:00 [revised] PHST- 2019/04/17 00:00 [accepted] PHST- 2019/05/08 06:00 [pubmed] PHST- 2020/06/10 06:00 [medline] PHST- 2019/05/08 06:00 [entrez] AID - 10.1002/jcp.28767 [doi] PST - ppublish SO - J Cell Physiol. 2019 Dec;234(12):22044-22056. doi: 10.1002/jcp.28767. Epub 2019 May 6.