Long non-coding RNA IGF2-AS represses breast cancer tumorigenesis by epigenetically regulating IGF2

Abstract

Long non-coding RNAs are a kind of endogenous ncRNAs with a length of more than 200 bp. Accumulating evidence suggests that long non-coding RNAs function as pivotal regulators in tumorigenesis and progression. However, their biological roles in breast cancer remain largely unknown. Here, we found that IGF2 antisense RNA (IGF2-AS) was significantly decreased in breast cancer tissues, cell lines, and plasma. Patients with low IGF2-AS were more likely to develop larger tumor size and later clinical stage. Overexpression of IGF2-AS evidently inhibited the proliferation and induced apoptosis of MCF-7 and T47D cells in vitro, as well as retarded tumor growth in vivo. Further investigation revealed that IGF2-AS inhibited the expression of its sense-cognate gene IGF2 in an epigenetic DNMT1-dependent manner, resulting in the inactivation of downstream oncogenic PI3K/AKT/mTOR signaling pathway. Enforced expression of IGF2 could significantly block the tumor inhibitory effect of IGF2-AS. Importantly, we found that IGF2-AS could be used as an effective biomarker for breast cancer diagnosis and prognosis. Taken together, our study indicates that IGF2-AS is a tumor suppressor in breast cancer, restoration of IGF2-AS may be a promising treatment for this fatal disease.

Over-expression of long non-coding RNA insulin-like growth factor 2-antisense suppressed hepatocellular carcinoma cell proliferation and metastasis by regulating the microRNA-520h/cyclin-dependent kinase inhibitor 1A signaling pathway

“…Collectively, these results indicated that IGF2-AS may serve as a tumor suppressor in HCC, a potential prognostic biomarker and therapeutic target for HCC patients. Our findings are in line with what have been reported in several other cancers including breast cancer [6], gastric cancer [7], CRC [8], and gastric adenocarcinoma [22].…”

“…Increasing studies have verified that long noncoding RNAs (lncRNAs) play key roles during the development of multiple human cancers [ 3–5 ]. Studies have reported that IGF2-AS is a biomarker for cancer diagnosis and prognosis, including as a tumor suppressor in breast cancer [ 6 ], a promotor of glycolysis and apoptosis of gastric cancer cells via targeting miR-195/CREB1 axis [ 7 ], a potential target for colorectal cancer (CRC) treatment [ 8 ], as well as the prognosis and metastasis of gastric adenocarcinoma via serving as a ceRNA of miR-503 to regulate SHOX2 9 . We identified that IGF2-AS was remarkably down-regulated in tumor tissues by analyzing the differentially expressed lncRNAs in HCC based on the RNA-seq dataset in TCGA database (14 tumor and 42 adjacent normal samples) ( Figure 1a ).…”

Identification of prognostic candidate signatures by systematically revealing transcriptome characteristics in lung adenocarcinoma with differing tumor microenvironment immune phenotypes

“…Some published results showed that some lncRNAs play an important regulatory role in the tumorigenesis of some cancers such as breast cancer, ovarian cancer, cervical cancer and so on. For example, the lncRNA IGF2-AS, as an antisense gene of IGF2, inhibits the tumorigenesis of breast cancer by epigenetically regulating IGF2 and affects the metastasis and prognosis of gastric adenocarcinoma by sponging miR-503 to regulate SHOX2 [28,29]. The lncRNA EMX2OS has been reported to affect the proliferation and invasion of ovarian cancer cells by sponging miR-654-3p to regulate AKT3 and the downregulation of EMX2OS results in a poor prognosis of patients with kidney renal clear cell carcinoma [30,31].…”

lncRNA IGF2‐AS promotes the osteogenic differentiation of bone marrow mesenchymal stem cells by sponging miR‐3,126‐5p to upregulate KLK4

“…Previously, lncRNA IGF2‐AS was extensively studied in human cancers 16 . Functionally, IGF2‐AS represses breast cancer tumorigenesis by epigenetically regulating IGF2 16 .…”

“…Previously, lncRNA IGF2‐AS was extensively studied in human cancers 16 . Functionally, IGF2‐AS represses breast cancer tumorigenesis by epigenetically regulating IGF2 16 . Moreover, IGF2‐AS regulates high‐glucose‐induced apoptosis in human retinal pigment epithelial cells 17 .…”