Long Noncoding RNA MEG3 Suppresses Glioma Cell Proliferation, Migration, and Invasion by Acting as a Competing Endogenous RNA of miR-19a

Abstract

Glioma, with varying malignancy grades and histological subtypes, is the most common primary brain tumor in adults. Long noncoding RNAs (lncRNAs) are non-protein-coding transcripts and have been proven to play an important role in tumorigenesis. Our study aims to elucidate the combined effect of lncRNA maternally expressed gene 3 (MEG3) and microRNA-19a (miR-19a) in human glioma U87 and U251 cell lines. Real-time PCR revealed that MEG3 was downregulated and miR-19a was upregulated in malignant glioma tissues and cell lines. Bioinformatics analyses (TargetScan, miRanda, and starBase V2.0) showed that phosphatase and tensin homolog (PTEN) is a target of miR-19a with complementary binding sites in the 3'-UTR. As expected, luciferase results verified the putative target site and also revealed the complementary binding between miR-19a and MEG3. miR-19a represses the expression of PTEN and promotes glioma cell proliferation, migration, and invasion. However, MEG3 could directly bind to miR-19a and effectively act as a competing endogenous RNA (ceRNA) for miR-19a to suppress tumorigenesis. Our study is the first to demonstrate that lncRNA MEG3 suppresses glioma cell proliferation, migration, and invasion by acting as a ceRNA of miR-19a, which provides a novel insight about the pathogenesis of glioma.

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

“…Reduced expression of MEG3 has been found in variety of cancers tissues and cell lines [7-11]. In our current study, we have demonstrated that MEG3 was low expressed in BON1 and QGP-1 cells when compared to HEK293, CCL-153, and EC-304 cell lines.…”

“…In addition, they are being identified and characterized for serial steps of cancer development, including tumor initiation, growth, and metastasis [6]. Maternally expressed gene 3 (MEG3), a lncRNA that has attracted much research interest, is aberrantly expressed in several human cancers including ovarian cancer [7], gastric cancer [8], colorectal cancer [9], cervical cancer [10], and malignant glioma [11]. Moreover, according to these previous studies, MEG3 exhibited anti-cancer effects via regulation of cell proliferation, apoptosis, and metastasis.…”

AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma

“…It is supposed that RNA transcripts communicate with others through “talking” with a new “language” mediated by miRNA response elements (MREs) . Qin et al reported that lncRNA MEG3 inhibited glioma cell proliferation, migration, and invasion by acting as a ceRNA of miR‐19a . Xiao et al reported that lncRNA TP73‐AS1 suppressed glioma growth and metastasis by working as a ceRNA through miR‐124‐dependent inhibitor of iASPP regulation .…”

“…12,13 Qin et al reported that lncRNA MEG3 inhibited glioma cell proliferation, migration, and invasion by acting as a ceRNA of miR-19a. 14 Xiao et al reported that lncRNA TP73-AS1 suppressed glioma growth and metastasis by working as a ceRNA through miR-124-dependent inhibitor of iASPP regulation. 15 Until now, it has been unclear whether AC016405.3 can act as a ceRNA and cowork with any miRNAs in GBM.…”

Long non‐coding RNA FEZF1‐AS1 promotes breast cancer stemness and tumorigenesis via targeting miR‐30a/Nanog axis

“…For decades, lncRNAs are regarded as the transcription “noise,” therefore, no further studies are contributed to the research. LncRNAs also regulate the tumor stem cell characteristics (Qin, Tong, Sun, & Xu, ; Zeng et al, ). For example, lncRNA HOTTIP is over‐expressed in human pancreatic cancer and HOTTIP variation regulates the pancreatic cancer stemness factors (LIN28, NANOG, OCT4, and SOX2) and stem markers (ALDH1, CD44, and CD133) by regulating HOXA9 and enhancing the Wnt/β‐catenin pathway by binding with WDR5 (Fu et al, ).…”