Orak Ghazal, Rezaei Hossein Babaahmadi, Ameli Fereshteh, Maghsoodi Fatemeh, Cheraghzade Maryam, Adelipour Maryam
Department of Clinical Biochemistry, School of Medicine Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran.
Hyperlipidemia Research Center Ahvaz Jundishapur University of Medical Science Ahvaz Iran.
Health Sci Rep. 2023 Sep 11;6(9):e1552. doi: 10.1002/hsr2.1552. eCollection 2023 Sep.
Breast cancer is a leading cause of incidence and mortality in women globally. Identifying new molecular markers can aid in cancer diagnosis, targeted therapy, and treatment monitoring. This study aimed to measure the expression of the X-box binding protein 1 (XBP1) gene, an index of the unfolded protein response (UPR), and long noncoding RNAs (lncRNAs), including Nuclear Enriched Abundant Transcript 1 (NEAT1), Cancer Susceptibility Candidate 2 (CASC2), and Long Intergenic Nonprotein Coding RNA 299 (LINC00299), as possible regulators of the UPR pathway.
Total RNA was extracted from 40 samples of breast tumor tissues and their respective controls. The expression level of lncRNAs CASC2, NEAT1, and LINC00299 was quantified using reverse transcription-polymerase chain reaction (RT-PCR). The ratio of the spliced form of XBP1 to its unspliced form (XBP1u) was determined by PCR and electrophoresis.
The results showed a 2.8-fold increase in the ratio of XBP1s/u in breast cancer tissues compared to adjacent nonmalignant samples ( < 0.05). Additionally, the level of lncRNAs NEAT1, CASC2, and LINC00299 in breast tumor tissues increased significantly by twofold, 1.5-fold, and 2.3-fold, respectively, compared to adjacent nonmalignant samples ( < 0.05).
Based on the association between the expression of lncRNAs CASC2, LINC00299, and NEAT1 and the XBP1s/u ratio, these lncRNAs could be potential regulators of the UPR pathway. Also, CASC2 and NEAT1 genes could be suggested as suitable biomarkers to distinguish cancerous tissue from noncancerous breast tissue due to their significant increase in expression in cancerous samples compared to adjacent noncancerous.
乳腺癌是全球女性发病和死亡的主要原因。识别新的分子标志物有助于癌症诊断、靶向治疗和治疗监测。本研究旨在检测X盒结合蛋白1(XBP1)基因(未折叠蛋白反应(UPR)的一个指标)以及长链非编码RNA(lncRNA)的表达,这些lncRNA包括核富集丰富转录本1(NEAT1)、癌症易感性候选基因2(CASC2)和长链基因间非编码RNA 299(LINC00299),它们可能是UPR通路的调节因子。
从40份乳腺肿瘤组织样本及其相应对照中提取总RNA。使用逆转录聚合酶链反应(RT-PCR)定量检测lncRNA CASC2、NEAT1和LINC00299的表达水平。通过PCR和电泳测定XBP1剪接形式与其未剪接形式(XBP1u)的比例。
结果显示,与相邻非恶性样本相比,乳腺癌组织中XBP1s/u的比例增加了2.8倍(P<0.05)。此外,与相邻非恶性样本相比,乳腺肿瘤组织中lncRNA NEAT1、CASC2和LINC00299的水平分别显著增加了2倍、1.5倍和2.3倍(P<0.05)。
基于lncRNA CASC2、LINC00299和NEAT1的表达与XBP1s/u比例之间的关联,这些lncRNA可能是UPR通路的潜在调节因子。此外,由于CASC2和NEAT1基因在癌组织中的表达与相邻非癌组织相比显著增加,因此可作为区分癌组织和非癌乳腺组织的合适生物标志物。