Abstract
We aimed to explore the interaction among lncRNA MALAT1, miR‐129 and SOX2. Besides, we would investigate the effect of MALAT1 on the proliferation of glioma stem cells and glioma tumorigenesis. Differentially expressed lncRNAs in glioma cells and glioma stem cells were screened out with microarray analysis. The targeting relationship between miR‐129 and MALAT1 or SOX2 was validated by dual‐luciferase reporter assay. The expressions of MALAT1, miR‐129 and SOX2 mRNA in both glioma non‐stem cells and glioma stem cells were examined by qRT‐PCR assay. The impact of MALAT1 and miR‐129 on glioma stem cell proliferation was observed by CCK‐8 assay, EdU assay and sphere formation assay. The protein expression of SOX2 was determined by western blot. The effects of MALAT1 and miR‐129 on glioma tumour growth were further confirmed using xenograft mouse model. The mRNA expression of MALAT1 was significantly up‐regulated in glioma stem cells compared with non‐stem cells, while miR‐129 was significantly down‐regulated in glioma stem cells. MALAT1 knockdown inhibited glioma stem cell proliferation via miR‐129 enhancement. Meanwhile, miR‐129 directly targeted at SOX2 and suppressed cell viability and proliferation of glioma stem cells by suppressing SOX2 expression. The down‐regulation of MALAT1 and miR‐129 overexpression both suppressed glioma tumour growth via SOX2 expression promotion in vivo. MALAT1 enhanced glioma stem cell viability and proliferation abilities and promoted glioma tumorigenesis through suppressing miR‐129 and facilitating SOX2 expressions.
Highlights
Glioma is one of the most prevalent and aggressive malignant tumours in human central nervous system with high mortality rate around the world.[1]
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was suspected to bind to miR-129 which target at SOX2, an oncogene, and their interaction was depicted in this study
MALAT1 siRNA, miR-129 mimics and miR-129 inhibitor were synthesized by Genepharma Company (Shanghai, China). 293T cells were respectively transfected with Long non-coding RNAs (lncRNAs) MALAT1 siRNA, miR-129 mimics, miR-129 inhibitor and negative control lncRNA MALAT1 or negative control mimics using LipofectamineTM 2000 reagent (Life Technologies Inc., USA) following the instructions
Summary
Glioma is one of the most prevalent and aggressive malignant tumours in human central nervous system with high mortality rate around the world.[1]. Long non-coding RNAs (lncRNAs), a group of non-protein coding transcripts longer than 200 nucleotides, play a key role in many types of malignant tumours, including glioma.[8]. Wang et al revealed that MALAT1 was aberrantly expressed in carcinoma cells.[10]. The role of miR-129 in glioma stem cells has not been elucidated so far. SRY (sex determining region Y)-box 2 (SOX2) is revealed as a stemness marker in glioma 19 and a transcription factor highly associated with pluripotency.[20]. Current study investigated the relationship between SOX2 and miR-129 to further elucidate the molecule network of miR-129 in glioma stem cells progression. SOX2 expression changes are significant for GSC stemness maintainment. MALAT1 was suspected to bind to miR-129 which target at SOX2, an oncogene, and their interaction was depicted in this study. By illustrating the underlying mechanism that facilitated glioma progression, this study may contribute to the application of glioma target therapy
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