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

Abstract

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 HER2negative 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. K E Y W O R D Sbreast cancer, lncRNA, mTOR

Long non-coding RNA SNHG3 promotes breast cancer cell proliferation and metastasis by binding to microRNA-154-3p and activating the notch signaling pathway

“…Result of RT-qPCR was consistent with that of transcriptome sequencing (p < 0.05) ( Fig. 1b) while SNHG3 expressed higher in estrogen receptor/progesterone receptor (ER/PR) compared with ER/PR positive BC [24]. However, there was less study about SNHG3 in BC.…”

<p>Latest Advances of Long Non-Coding RNA SNHG5 in Human Cancers</p>

“…SNHG5, a relatively novel lncRNA, was attached to more and more attention due to its distinct biological and clinical effects in human cancers. Concluding from current clinical investigation results, SNHG5 overexpression was detected in multiple human cancers, including glioma, 20,24 acute myeloid leukemia, 37 breast cancer, 25,28 melanoma, 15,39 colorectal cancer, 16,21 osteosarcoma, 17,40 hepatocellular carcinoma 30 and bladder cancer. 23 In these cancers, SNHG5 could serve as an oncogene in tumor size, pathological stage, recurrence rate and overall survival.…”

“…[25][26][27] Zahra et al also confirmed that SNHG5 was involved in cancer stage, overall grade, mitotic rate and tumor size in BRCA patients. 28 Notably, SNHG5 was detected to correlate with positive reaction of estrogen receptor, progesterone receptor and Her2/neu expression, 28 which were main subtypes of BRCA patients. 29 Besides, SNHG5 knockdown inhibited proliferation and induced apoptosis, cell-cycle arrest at G1 phases in BRCA cells.…”

LncRNA SNHG3, a potential oncogene in human cancers

“…Wang et al [ 33 ] found that SNHG3 silencing enhances apoptosis in triple-negative breast cancer (TNBC) cells through the miR-326/integrin α5 (ITGA5) axis and inhibits cell viability, migration, invasion and the Vav2/Rac1 signaling pathway. These results demonstrated that SNHG3 acts as an oncogenic lncRNA in breast cancer, which may represent a potential diagnostic biomarker or a novel therapeutic target for cancers [ 34 ].…”