Assessment of the expression pattern of mTOR‐associated lncRNAs and their genomic variants in the patients with breast cancer

• Published in: Journal of cellular physiology 2019-12, Vol.234 (12), p.22044-22056
• Main Authors: Taherian‐Esfahani, Zahra, Taheri, Mohammad, Dashti, Sepideh, Kholghi‐Oskooei, Vahid, Geranpayeh, Lobat, Ghafouri‐Fard, Soudeh
• Format: Article
• Language: English
• Subjects: Breast cancer; Contraceptives; Diagnostic systems; ErbB-2 protein; Estrogen receptors; Estrogens; Gene expression; Gene mapping; Genes; Genotypes; lncRNA; Menopause; mTOR; Nucleoli; Pathogenesis; Peripheral blood; Progesterone; Quantitative trait loci; Rapamycin; Signal transduction; snoRNA; Tissues; TOR protein; Transcription; Tumors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28767

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. In the current investigation, we demonstrated dysregulation of small nucleolar RNA host genes (SNHGs) in breast cancer tissues in correlation with tumor features. The current study underscores the significance of SNHGs in the pathogenesis of breast cancer.