LncRNA TMPO‐AS1 promotes LCN2 transcriptional activity and exerts oncogenic functions in ovarian cancer

Abstract

Ovarian cancer remains the sixth most frequently occurring cancer in women worldwide. Long noncoding RNAs (lncRNAs) are capable of regulating gene expression, and thus, participating in a wide range of biological functions and disease processes including cancer development. Our work suggests that lncRNA TMPO antisense RNA 1 (TMPO‐AS1) represents an oncogenic lncRNA in ovarian cancer and presents a novel mechanism involving transcription factor E2F transcription factor 6 (E2F6) and lipocalin‐2 (LCN2). We identified upregulated lncRNA TMPO‐AS1 in ovarian cancer tissues and cells. siRNA‐mediated silencing of lncRNA TMPO‐AS1 restrained the aggressiveness of ovarian cancer cells and their pro‐angiogenic ability, and reduced the expression of LCN2. LncRNA TMPO‐AS1 was found to interact with E2F6, a transcriptional repressor that could bind to the promoter region of LCN2 gene. In addition, silencing of E2F6 or overexpression of LCN2 restored the aggressiveness of ovarian cancer cells and their pro‐angiogenic ability following siRNA‐mediated silencing of lncRNA TMPO‐AS1. Taken together, we demonstrated lncRNA TMPO‐AS1 could potentially promote LCN2 transcriptional activity by binding to transcription factor E2F6, and thus, stimulated the progression of ovarian cancer. These findings underscore a possible alternative therapeutic strategy for ovarian cancer treatment.

The Emerging Role of Thymopoietin-Antisense RNA 1 as Long Noncoding RNA in the Pathogenesis of Human Cancers

“…LncRNAs are also involved in DNA repair, cell proliferation, and EMT through regulating the expression of various genes linked to carcinogenesis and tumor progression. TMPO-AS1 was demonstrated to have abnormal expression in breast cancer (Mitobe et al, 2020), cervical cancer (Zhao et al, 2020), and ovarian cancers (Li et al, 2020a). In triple-negative breast cancer, the upregulation of TMPO-AS1 was associated with tumor proliferation-related biomarkers.…”

“…TMPO-AS1 was reported to be significantly upregulated in various cancers, such as lung cancer (Yu et al, 2020), breast cancer (Mitobe et al, 2020), colorectal cancer (CRC) (Mohammadrezakhani et al, 2020), hepatocellular carcinoma (HCC) (Liu and Shen, 2020;Wang et al, 2020), gastric cancer (GC) (Sun and Han, 2020), bladder cancer (He et al, 2020b), laryngeal squamous cell carcinoma (LSCC) (Zhang et al, 2020b), ovarian cancer (Li et al, 2020a;Zhao et al, 2020), thyroid cancer (Li et al, 2020b), esophageal cancer (Gao et al, 2020), Wilms tumor (Zhang et al, 2020a), cervical cancer (Gang et al, 2020), retinoblastoma (Peng et al, 2020), osteosarcoma (Cui and Zhao, 2020), or prostate cancer (Huang et al, 2018), and functions as an oncogene in carcinogenesis and tumor progression. To further investigate the aberrant expression of TMPO-AS1 in various cancers and their associated prognosis, this study applied the Gene Expression Profiling Interactive Analysis (GEPIA) online data analysis tool (Tang et al, 2017).…”

<p>LncRNA TMPO-AS1 Promotes Proliferation and Invasion by Sponging miR-383-5p in Glioma Cells</p>

“…6 Zhao et al reported that silence of TMPO-AS1 restrained the aggressiveness and the pro-angiogenic activity of ovarian cancer cells, blocking ovarian cancer development. 17 In the present study, we first discovered the increase of lncRNA-TMPO-AS1 in glioma cell lines, and further cellular function assay disclosed that knockdown of TMPO-AS1 could suppress glioma cell proliferation, colony formation, migration and invasion, demonstrating the oncogenic activity of TMPO-AS1 in glioma. The crosstalk between lncRNAs and miRNAs is common in cancer biology.…”

The Interplay between Long Noncoding RNAs and Proteins of the Epigenetic Machinery in Ovarian Cancer

“…The authors demonstrated that DLX6-AS1 acts by sponging the miR-195-5p and upregulating its miRNA-target FHL2 (four and a half LIM domains 2). Likewise, TMPO-AS1 (thymopoietin antisense RNA 1) knockdown significantly suppressed OC cell proliferation, migration, invasion, and angiogenesis, also inhibiting tumorigenesis and angiogenesis in vivo [26]. TMPO-AS1 was found to be upregulated in OC cell lines and clinical samples and exerts its oncogenic role by binding to E2F6 (E2F transcription factor 6) and modulating its occupancy on the promoter region of LCN2 (lipocalin 2), whose expression is activated.…”

“…The interplay between differentially expressed lncRNAs, such as MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and CDKN2B-AS1 (cyclin-dependent kinase inhibitor 2B antisense RNA 1), and histone-modifying or chromatin-remodeling complexes has been implicated in transcriptional regulation, enabling progression of different cancer types [24]. A set of the OC-related lncRNAs acts as oncogenes or tumor suppressors, contributing to cellular transformation [25][26][27].…”