Inhibited Glioma Cell Migration Research Articles

From single-cell to spatial transcriptomics: decoding the glioma stem cell niche and its clinical implications

BackgroundGliomas are aggressive brain tumors associated with a poor prognosis. Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature.MethodsSingle-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature.ResultsA distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo.ConclusionThis study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and identify potential therapeutic targets, particularly TUBA1C, aimed at improving patient outcomes.

LncRNA LINC01140 Inhibits Glioma Cell Migration and Invasion via Modulation of miR-199a-3p/ZHX1 Axis [Retraction

[This retracts the article DOI: 10.2147/OTT.S230895.].

Retracted] miR‑216b inhibits glioma cell migration and invasion through suppression of FoxM1.

Following the publication of the above article, a concerned reader reported that certain of the cell invasion assay data shown in Fig. 2D, and the mouse images shown in Fig. 6A, were strikingly similar to data that appeared in the following (subsequently published) article: Li C, Zheng H, Hou W, BaoH, Xiong J, Che W, Gu Y, Sun H and Liang P: Long non-coding RNA linc00645 promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis 10: 717, 2019. The authors regret that the data in question featured in the original Oncology Reports article had been re-used, and accept the Editor's decision to retract this article; furthermore, the authors and the Editor apologize to the readership of the Journal for any inconvenience caused. [Oncology Reports 38: 1751‑1759, 2017; DOI: 10.3892/or.2017.5824].

Berberine inhibits glioma cell migration and invasion by suppressing TGF-β1/COL11A1 pathway

Glioma is a clinically heterogeneous disease with a poor prognosis. Berberine (BBR), as a multi-target anti-tumor alkaloid, has the ability to penetrate the blood-brain barrier and shows cytotoxicity to glioma cells. In previous studies, we demonstrated that berberine inhibits glioma cell proliferation by inhibiting mutant p53 protein and promoting mitochondrial damage. In addition, berberine has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on collagen in cancer needs to be further elucidated. In this study, we proved that the collagen XI alpha 1 chain (COL11A1) is highly expressed in glioma cell lines and associated with migration and invasion of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-β1/COL11A1 pathway and changes actin cytoskeleton arrangement. Nude mouse subcutaneous xenografts model also showed that berberine inhibited the expression of COL11A1 in vivo. Collectively, berberine that targets COL11A1 to inhibit glioma migration and invasion, may serve as a promising candidate for the development of anti-glioma drugs in the future.

GLI1 is involved in HIF-1α-induced migration, invasion, and epithelial-mesenchymal transition in glioma cells.

Glioma is characterized by hypoxia that activates the hypoxia inducible factor (HIF) pathway and controls a myriad of genes that drive cancer progression. HIF-1α promotes GLI1 transferring to the nucleus by activating the hedgehog pathway under hypoxic conditions. However, their mechanisms in glioma cells under hypoxia remain unknown. Human glioma cell lines (LN229 and LN18) were transfected with HIF-1α or GLI1-specific short hairpin RNAs (shRNAs) and cultured under normoxic or hypoxic conditions. The protein levels of HIF-1α, GLI1, and epithelial-mesenchymal transition (EMT) markers including E-cadherin and vimentin were measured by Western blot analysis. RT-qPCR analysis was performed for the detection of HIF-1α and GLI1 mRNA expression. Cell migratory and invasive capacities were evaluated by wound healing and Transwell assays, respectively. Hypoxia blocked the breakdown of the HIF-1α protein and upregulated GLI1 expression in glioma cells. Downregulation of HIF-1α expression inhibited hypoxia-induced cell migration and invasion, as well as reversed the effects of hypoxia on GLI1, E-cadherin, and vimentin expression in LN229 and LN18 cells. Depletion of GLI1 inhibited glioma cell migration and invasion induced by hypoxia. Silenced GLI1 did not affect HIF-1α expression but completely offset hypoxia-regulated expression of E-cadherin and vimentin in glioma cells. GLI1 is involved in HIF-1α-induced migration, invasion, and EMT in glioma cells, thus revealing a novel molecular mechanism for glioma research.

Long Non-Coding RNA HCG11 Inhibits Glioma Cells Proliferation and Migration through Decoying miR-590-3p and Up-Regulating CADM2

Background: Long non-coding RNAs are reportedly endowed with the function of promoting or inhibiting cancer occurrence and development. The emphasis of this study was placed on the effect of lncRNA HLA complex group 11 (HCG11) on glioma progression, as well as its mechanism. Methods: Quantitative real-time polymerase chain reaction was utilized for detecting HCG11, miR-590-3p, and CAMD2 mRNA expression levels in glioma tissues. Western blot was adopted to examine cell adhesion molecule (CADM2) protein expression. Cell counting kit-8, BrdU, Transwell and wound healing assays were employed for investigating the malignant biological behaviors of glioma cells. RNA immunoprecipitation assay and dual-luciferase reporter assay were performed to prove the relationship between miR-590-3p and HCG11, as well as CADM2 and miR-590-3p. Results: HCG11 expression was lower in glioma tissues compared with that in paracancerous tissues, and its expression level was negatively correlated with WHO tumor stage. In addition, compared with in astrocyte cell line, the expression of HCG11 was lower in glioma cells. Functional experiments showed that HCG11 inhibited glioma cells migration and proliferation, while miR-590-3p facilitated these processes. Acting as a competitive endogenous RNA, HCG11 adsorbed miR-590-3p and upregulated the expression of CADM2, the target gene of miR-590-3p. Conclusions: HCG11 suppresses glioma cells proliferation and migration through regulating the miR-590-3p/CADM2 molecular axis.

MicroRNA-3148 inhibits glioma by decreasing DCUN1D1 and inhibiting the NF-kB pathway.

Glioma, which originates in the brain, is the most aggressive tumor of the central nervous system. It has been shown that microRNA (miRNA) controls the proliferation, migration and apoptosis of glioma cells. The objective of the present study was to measure microRNA-3148 (miR-3148) expression and investigate its impact on the pathogenetic mechanism of glioma. In the present study, reverse transcription-quantitative real-time PCR was employed to detect miR-3148 expression levels in glioma tissues and cell lines. Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and Transwell migration assay were performed to assess the influence of miR-3148 on the malignant biological behavior of glioma cells. The biological functions of miR-3148 in glioma were examined via a xenograft tumor growth assay. Furthermore, the association between miR-3148 and DCUN1D1 was investigated via immunohistochemistry, dual-luciferase reporter assay and western blotting. It was observed that miR-3148 was expressed at low levels in glioma cells, and this represented a poor survival rate. In addition, an increased level of miR-3148 in cells and animal models inhibited glioma cell migration and proliferation. Moreover, miR-3148 decreased DCUN1D1 and curbed the nuclear factor κ enhancer binding protein (NF-κB) signaling pathway, thus decreasing the growth of glioma. Thus, miR-3148 is expressed within glioma tissues at low levels where it suppresses glioma by curbing the NF-κB pathway and lowering DCUN1D1.

Knockdown of DCLK1 Inhibits Proliferation, Migration and Invasion of Glioma Cells

Knockdown of DCLK1 Inhibits Proliferation, Migration and Invasion of Glioma Cells

Downregulation of USP33 inhibits Slit/Robo signaling pathway and is associated with poor patient survival of glioma.

Gliomas are the most common malignant tumors in the central nervous system originating from brain glial cells. Although characterized as highly invasive and highly malignant, few molecular targeting therapies have been developed. Ubiquitin Specific Protease 33 (USP33), a gene encoding a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling, participates in the development of several malignant tumors, however, its role in the development of glioma has not been evaluated. Real-time quantitative PCR was performed to examine the expression of USP33 in glioma tissues and cell lines. Immunohistochemistry was performed to determine USP33 expressions in glioma tissue microarray. Transwell assay was performed to analyze the effect of USP33 on glioma cell line migration. The Kaplan-Meier method and log rank test were applied to evaluate the prognostic value of USP33 expression. Univariate and multivariate Cox proportional hazard regression models were used to identify the independent prognostic factors associated with overall survival (OS) or disease-free survival. The present study demonstrated that USP33 expression was significantly downregulated in glioma tissues. Lower expression of USP33 was associated with a poorer patient disease-free survival and overall survival. In vitro studies revealed that overexpression of USP33 significantly inhibited the migration ability of glioma cells. Mechanistically, USP33 inhibits glioma cell migration by regulating the function of Slit/Robo signaling pathway. Downregulation of USP33 is associated with poor patient survival of glioma. USP33 inhibits glioma cell migration by Slit/Robo signaling pathway. This mechanism may be applied for development of targeting therapy especially for the high-grade glioma.

The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1.

Objective: The role of lncRNAs in tumor has been widely concerned. The present study took HAS2-AS1 (the antisense RNA 1 of HAS2) as a starting point to explore its expression in glioma and its role in the process of migration and invasion, providing a strong theoretical basis for mining potential therapeutic targets of glioma.Methods: Clinical data of glioma were obtained from The Cancer Genome Atlas (TCGA) database and differentially expressed lncRNAs were analyzed by edgeR. The hTFtarget database was used to predict the upstream transcription factors of HAS2-AS1 and the JASPAR website was used to predict the binding sites of human upstream transcription factor 1 (USF1) and HAS2-AS1. qRT-PCR was used to detect the expressions of HAS2-AS1 and USF1 in glioma tissues and cell lines. The effects of silencing HAS2-AS1 on the migration and invasion of cancer cells were verified by wound healing and Transwell invasion assays. The chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were applied to demonstrate the binding of USF1 and HAS2-AS1 promoter region. Western blot was used to detect the expressions of epithelial–mesenchymal transition (EMT)-related proteins.Results: HAS2-AS1 was highly expressed in glioma tissues and cells, and was significantly associated with poor prognosis. Silencing HAS2-AS1 expression inhibited glioma cell migration, invasion and EMT. USF1 was highly expressed in glioma and positively correlated with HAS2-AS1. The transcription of HAS2-AS1 was activated by USF1 via binding to HAS2-AS1 promoter region, consequently potentiating the invasion and migration abilities of glioma cells.Conclusion: These results suggested that the transcription factor USF1 induced up-regulation of lncRNA HAS2-AS1 and promoted glioma cell invasion and migration.

RIOK2 is negatively regulated by miR-4744 and promotes glioma cell migration/invasion through epithelial-mesenchymal transition.

RIOK2 is a member of RIO (right open reading frame) kinase family. Recent studies have revealed the involvement of RIO kinases in glioma cell growth and expansion. However, the role and mechanism of RIOK2 in glioma cell migration and invasion remain unclear. Wound healing assay, Transwell assay and real‐time quantitative PCR (qRT‐PCR) detection of matrix metalloproteinases (MMPs) were used to evaluate the migration/invasion of glioma cells. Western blot and qRT‐PCR were employed to measure the expression of epithelial‐mesenchymal transition (EMT) markers. Dual luciferase reporter assay was performed to determine the binding between RIOK2 and miR‐4744. In addition, RIOK2 and miR‐4744 levels were quantified by qRT‐PCR and/or immunohistochemistry in glioma tissues. Transfection of RIOK2 siRNAs significantly inhibited glioma cell migration and invasion and down‐regulated the expression of MMPs (MMP2 and MMP9) and mesenchymal markers (N‐cadherin, β‐catenin, Twist1, fibronectin, ZEB‐1) in glioma cells. Overexpression of RIOK2 showed the opposite effects. MiR‐4744 directly bound to the 3'‐untranslated region of RIOK2 and negatively regulated the expression of RIOK2. Up‐regulation of miR‐4744 inhibited the migration and invasion of glioma cells. Overexpression of RIOK2 could reverse the effects of miR‐4744 up‐regulation on the migration, invasion and EMT process in glioma cells. Moreover, RIOK2 was high, while miR‐4744 was low in glioma tissues, and a negative correlation was found between them. These results suggest that RIOK2 is post‐transcriptionally targeted by miR‐4744, the low miR‐4744 and high RIOK2 levels in glioma may contribute to tumour cell infiltration through promoting the EMT.

MiR-483 Targeted SOX3 to Suppress Glioma Cell Migration, Invasion and Promote Cell Apoptosis.

ObjectiveGlioma is the most common malignant brain tumor that has high aggressiveness. The aim of this study was to investigate the potential therapeutic targets for gliomas.Materials and MethodsReal-time quantitative polymerase chain reaction (RT-qPCR) was employed to calculate the expression of miRNA and genes. The connection between the expression of miR-483 and patients’ overall survival rate was evaluated using Kaplan–Meier analysis. In addition, the underlying mechanism was detected using luciferase assay.ResultsThe expression level of miR-483 was significantly decreased in glioma tissue samples and cell lines, compared to the adjacent tissues and normal cell lines. Downregulation of miR-483 or upregulation of SOX3 was associated with overall survival of glioma patients. Additionally, overexpression of miR-483 promotes cell invasion and migration and inhibits apoptosis. In addition, miR-483 directly targeted to SOX3, and the expression of miR-483 has a negative correlation with SOX3 in glioma tissues. SOX3 reversed partial functions of miR-483 on cell migration, invasion, and promoted cell apoptosis in glioma.ConclusionMiR-483 inhibited glioma cell migration, invasion, and promoted glioma cell apoptosis by targeting SOX3. MiR-483 maybe acted as a potential target for the treatment of glioma.

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis.

Background: Glioma is the most common malignant tumor of the central nervous system, and often displays invasive growth. Recently, circular RNA (circRNA), which is a novel non-coding type of RNA, has been shown to play a vital role in glioma tumorigenesis. However, the functions and mechanism of lipocalin-2 (Lcn2)-derived circular RNA (hsa_circ_0088732) in glioma progression remain unclear.Methods: We evaluated hsa_circ_0088732 expression by fluorescence in situ hybridization (FISH), Sanger sequencing, and PCR assays. Cell apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Transwell migration and invasion assays were performed to measure cell metastasis and viability. In addition, the target miRNA of hsa_circ_0088732 and the target gene of miR-661 were predicted by a bioinformatics analysis, and the interactions were verified by dual-luciferase reporter assays. RAB3D expression was analyzed by an immunochemistry assay, and E-cadherin, N-cadherin, and vimentin protein expression were examined by western blot assays. A mouse xenograft model was developed and used to analyze the effects of hsa_circ_0088732 on glioma growth in vivo.Results: We verified that hsa_circ_0088732 is circular and highly expressed in glioma tissues. Knockdown of hsa_circ_0088732 induced glioma cell apoptosis and inhibited glioma cell migration, invasion, and epithelial-mesenchymal transition (EMT). We found that hsa_circ_0088732 negatively regulated miR-661 by targeting miR-661, and RAB3D was a target gene of miR-661. In addition, inhibition of miR-661 promoted glioma cell metastasis and suppressed cell apoptosis. Knockdown of RAB3D induced cell apoptosis and suppressed cell metastasis. Moreover, hsa_circ_0088732 accelerated glioma progression through its effects on the miR-661/RAB3D axis. Finally, results from a mouse xenograft model confirmed that knockdown of hsa_circ_0088732 induced miR-661 expression, resulting in suppression of RAB3D expression and inhibition of tumor growth in vivo.Conclusion: We demonstrated that hsa_circ_0088732 facilitated glioma progression by sponging miR-661 to increase RAB3D expression. This study provides a theoretical basis for understanding the development and occurrence of glioma, as well as for the development of targeted drugs.

LncRNA LINC01140 Inhibits Glioma Cell Migration and Invasion via Modulation of miR-199a-3p/ZHX1 Axis.

PurposeGlioma is an aggressive tumor from the nervous system, which causes more than 70% of primary malignant brain tumors. Considering its severe malignancy, there is an urgent need to investigate more practical markers to understand the pathogenesis of glioma, and potential treatment methods for glioma patients. In the paper, we are focused on examining the roles of LINC01140, miR-199a-3p, and ZHX1 in the progression of gliomas, as well as their inner associations and modulation mechanisms.MethodsqRT-PCR was employed to examine the expression levels of LINC01140 and miR-199a-3p. We measured the expressions of ZHX1 via qRT-PCR and Western blotting. CCK8 assays, migration assays, and invasion assays were carried out to determine the cell viabilities and abilities of migration and invasion. We also conducted in vivo tumor growth experiments to investigate the roles of LINC01140 in glioma developments.ResultsThe expressions of LINC01140 were promoted in glioma. Silencing LINC01140 could inhibit glioma cell viabilities, migration, and invasion. In our experiments, miR-199a-3p was inhibited in glioma. LINC01140 negatively regulated the expressions of miR-199a-3p in glioma. MiR-199a-3p could target ZHX1 to inhibit its expression in glioma cells.ConclusionLINC01140 could promote glioma developments by modulating the miR-199a-3p/ZHX1 axis.

Nitidine Chloride Is a Potential Alternative Therapy for Glioma Through Inducing Endoplasmic Reticulum Stress and Alleviating Epithelial-Mesenchymal Transition

Background: Malignant glioma is a lethal brain tumor that is highly resistant to standard therapy. Our research aims to explore the suppressive effects of nitidine chloride (NC) on gliomas and the mechanisms involved, showing that it is a potential agent for integrative therapy of gliomas. Methods: After glioma cells were treated with NC, several experiments were performed to evaluate NC’s antitumor effects. CCK-8 assay was used to detect viability. Transwell and 3-dimensional spheroid invasion assays were used to evaluate motility of glioma in vitro, and the sphere-formation assay showed NC’s influence on glioma stem cells. Apoptosis and intracellular reactive oxygen species were measured by means of flow cytometry. Subcellular structures were observed through transmission electron microscopy. Western blot analysis reflected expression of endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) marker proteins. An orthotopic xenograft model was established to investigate the tumor suppressive effects in vivo. Results: Nitidine chloride inhibited glioma cell migration and invasion in vitro, downregulated the EMT proteins, and suppressed sphere formation of glioma stem cells. Furthermore, NC induced persistent ER stress that contributed to apoptosis and reactive oxygen species production. The xenograft model showed that NC effectively restricted glioma growth and invasion in vivo. Furthermore, we confirmed the signaling pathways that ER stress downregulates C/EBPβ and slug, as well as inhibition of the AKT/GSK3β/β-catenin axis caused by NC, in U-87 MG. Conclusion: We demonstrated that NC inhibits gliomas in vitro and in vivo by activating ER stress and downregulating EMT, which provides a basis for glioma therapy.

MiR‑143 acts as a novel Big mitogen‑activated protein kinase 1 suppressor and may inhibit invasion of glioma.

Upregulation of the Big mitogen‑activated protein kinase (BMK)1 has been reported in glioma and other epithelial tumors. In addition, the decreased expression of BMK1 inhibits tumorigenesis, leading to the broad consensus that it functions as cell‑autonomous epithelial tumor promoter. Using two online miRNA target prediction databases, microRNA (miR)‑143 was predicted as the potential miRNA regulator of BMK1. RNA immunoprecipitation analysis and Luciferase reporter assay showed that miR‑143 binds to the 3' untranslated region of BMK1. Notably, the expression of miR‑143 has a strong association with the World Health Organization grade and survival rates in patients with glioma by statistical analysis. Furthermore, miR‑143 inhibited glioma cells migration and invasion through cytoskeletal rearrangement in vitro and in vivo through matrigel invasion assay, scratch assay, cellular F‑actin measurement, chemotaxis assay and intracranial brain tumor xenografts. Finally, DNA methylation assay showed that the downregulation of miR‑143 was due to hypermethylation of its promoter region. These results reveal that miR‑143 represents a potential therapeutic target in glioma by modulating BMK1.

LncRNA NEF inhibits glioma by downregulating TGF-β1.

NEF is a tumor suppressing long non-coding (lnc)RNA in hepatocellular carcinoma. Based on current literature, the involvement of NEF in other human diseases is still unknown. The current study aimed to investigate the potential involvement of NEF in glioma, which is a type of rare, but aggressive malignancy. It was determined that NEF expression was downregulated in tumor tissues compared with adjacent heathy tissues. A low blood NEF level in patients with glioma effectively distinguished patients from healthy controls who had high blood NEF levels. Blood NEF levels were significantly correlation with distant tumor metastasis, but not tumor growth. Blood NEF levels were negatively correlated with blood transforming growth factor (TGF)-β1 levels in patients with distant tumor metastasis, but not in patients with non-metastatic glioma and healthy controls. NEF overexpression inhibited cancer cell migration and invasion. In addition, NEF overexpression downregulated TGF-β1 expression. The authors of the current study concluded that lncRNA NEF may inhibit glioma cell migration and invasion by downregulating TGF-β1.

Myosin Heavy Chain 10 (MYH10) Gene Silencing Reduces Cell Migration and Invasion in the Glioma Cell Lines U251, T98G, and SHG44 by Inhibiting the Wnt/β-Catenin Pathway

BackgroundThe myosin heavy chain 10 or MYH10 gene encodes non-muscle myosin II B (NM IIB), and is involved in tumor cell migration, invasion, extracellular matrix (ECM) production, and epithelial-mesenchymal transition (EMT). This study aimed to investigate the effects of the MYH10 gene on normal human glial cells and glioma cell lines in vitro, by gene silencing, and to determine the signaling pathways involved.Material/MethodsThe normal human glial cell line HEB, and the glioma cell lines, U251, T98G, and SHG44 were studied. Plasmid transfection silenced the MYH10 gene. The cell counting kit-8 (CCK-8) assay evaluated cell viability. Cell migration and invasion were evaluated using scratch and transwell assays. Western blot measured the protein expression levels, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels, for MYH10, metastasis-associated protein 1 (MTA-1), matrix metalloproteinase (MMP)-1, MMP-9, tissue inhibitor of metalloproteinases 2 (TIMP2), collagen 1, E-cadherin, vimentin, Wnt3a, β-catenin, and cyclin D1.ResultsThe MYH10 gene was overexpressed in U251, T98G, and SHG44 cells. MYH10 expression was down-regulated following siMYH10 plasmid interference, which also inhibited glioma cell migration and invasion. MYH10 gene silencing resulted in reduced expression of MTA-1, MPP-2, MMP-9 and vimentin, and increased expression of TIMP-2, E-cadherin and collagen 1 at the protein and mRNA level, and inhibited the Wnt/β-catenin pathway.ConclusionsIn human glioma cell lines, silencing the MYH10 gene reduced cell migration and invasion, by inhibiting the Wnt/β-catenin pathway, which may regulate the ECM and inhibit EMT in human glioma.

Expression and function of CDCA7L in gliomas

Objectives To analyze the expression and function of cell division cycle-associated 7-like protein (CDCA7L) in gliomas and to investigate the biological processes and signal pathway involved in glioma cells by CDCA7L. Methods The clinical data and CDCA7L expression information of 309 glioma patients were collected retrospectively from the CGGA mRNA sequencing data. TCGA mRNA sequencing was used as validation sets. Kaplan-Meier method and log-rank test were used to estimate the role of CDCA7L in the prognosis of patients. Gene ontology (GO) and KEGG pathway analysis were used to obtain biological processes and signal pathway involved in CDCA7L expression. Transwell chamber assay was used to detect the effect of knockdown of CDCA7L protein on migration of glioma cell lines. Flow cytometry was used to analyze the effect of knockdown of CDCA7L protein on glioma cell line apoptosis. Results CDCA7L was significantly upregulated along with tumor grades progress of glioma [0.053 (0.051), 0.083 (0.078)and 0.133 (0.152), respectively from WHO Ⅱ to Ⅳ, all P<0.05]. The expression of CDCA7L was higher in IDH wild-type gliomas [0.123 (0.165)and 0.068 (0.068), P<0.001]. Survival analysis revealed that high expression of CDCA7L indicated a poor survival outcome (P<0.001). Knockdown of CDCA7L inhibited glioma cell migration and promoted apoptotic (all P<0.01). Conclusions CDCA7L may be associated with the biological processes and signal pathway of glioma such as cell cycle, cell division, DNA replication, DNA repair and chromosome segregation. CDCA7L could promote the development of glioma and thus be used as a prognostic indicator and a potential therapeutic target. Key words: Glioma; Cell cycle proteins; Gene expression; Prognosis; Therapeutic target

MiR-361-5p inhibits glioma migration and invasion by targeting SND1.

BackgroundDownregulation of miR-361-5p contributes to epithelial–mesenchymal transition of glioma cells. However, the relevance of miR-361-5p to migration and invasion of gliomas remains unknown.Materials and methodsThe relationship between miR-361-5p and SND1 expression was analyzed in 120 human gliomas and 8 glioma cell lines by in situ hybridization, immunohistochemistry, and Western blot. Dual-luciferase reporter assay was used to identify SND1 as a target of miR-361-5p. The mechanisms through which miR-361-5p inhibits glioma cell migration and invasion were studied by in vitro assays.ResultsmiR-361-5p expression was significantly downregulated in glioma tissues and glioma cell lines, and was inversely correlated with glioma grades. However, SND1 expression was positively correlated with glioma grades and inversely correlated with miR-361-5p expression. miR-361-5p overexpression suppressed glioma cell migration and invasion through targeting SND1 and subsequently decreasing MMP-2 expression. In glioma cell lines, SND1 overexpression could partly reverse the antitumor effects of miR-361-5p.ConclusionThe findings provide evidence that miR-361-5p directly targets SND1 to degradation and then reduces MMP-2 gene transcription, thus inhibiting glioma migration and invasion. miR-361-5p is an important tumor suppressor and a novel diagnostic biomarker of glioma, and miR-361-5p and SND1 are potential therapeutic candidates for malignant gliomas.