Expression Analysis of MALAT1, GAS5, SRA, and NEAT1 lncRNAs in Breast Cancer Tissues from Young Women and Women over 45 Years of Age

Abstract

Breast cancer, as the most common cancer in women worldwide, represents about 30% of all cancers affecting women. Long non-coding RNAs (lncRNAs) have been implicated in the regulation of several biological processes, and their dysregulation in cancer has well been documented. To investigate possible age-dependent variations in expression profiles of lncRNAs, we evaluated the expression levels of four lncRNAs, i.e., MALAT1, GAS5, SRA, and NEAT1, in breast cancer (BC) samples obtained from younger (45 years) women. Tumor samples (n = 23) and 15 normal tissues were collected from BC patients. All tumor and normal samples were morphologically confirmed by a pathologist. RNA was extracted from the tissues and cDNAs were then synthesized. The lncRNA expression levels were evaluated by qRT-PCR. The changes in the expression levels were determined using the ΔΔCt method. Compared to normal tissues, BC tissues from both age groups (women under 45 years of age and women above 45 years of age) showed upregulation of MALAT1 (p = 0.003 and p = 0.0002), SRA (p = 0.005 and p = 0.0002), and NEAT1 (p = 0.010 and p = 0.0002) and downregulation of GAS5 (p = 0.0002 and p = 0.0005). Additionally, our analysis showed significant and direct correlation between the age and the expression levels of three of the four lncRNAs studied in this work. All four lncRNAs were overexpressed in both MDA-MB-231 and MCF7 cell lines (p = 0.1000). Our data show that MALAT1, GAS5, SRA, and NEAT1 lncRNAs are dysregulated in BC samples. However, except for MALAT1, the expression levels of all of these lncRNAs were significantly lower in cancers developed in younger cases, where poorer prognosis is suggested. Of note, GAS5 reduced expression has been documented to correlate with tumor progression. Keywords: breast cancer, lncRNAs, MALAT1, GAS5, SRA, NEAT1, age, Iran