Gene Expression Profile Identifies LncRNA AL355974.3 As a Potential Glioma Biomarker

Abstract

Objective

Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients.

Methods

First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.

Results

RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes.

Conclusion

Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.

References

[1] Ostrom QT, Price M, Neff C, et al.. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016–2020. Neuro Oncol, 2023, 25(12): iv1-iv99 Suppl 2

[2] Weller M, van den Bent M, Hopkins K, et al.. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol, 2014, 15(9): e395-e403

[3] Yang K, Wu Z, Zhang H, et al.. Glioma targeted therapy: insight into future of molecular approaches. Mol Cancer, 2022, 21(1): 39

[4] Ceccarelli M, Barthel FP, Malta TM, et al.. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell, 2016, 164(3): 550-563

[5] Ulitsky I, Bartel DP. lincRNAs: Genomics, Evolution, and Mechanisms. Cell, 2013, 154(1): 26-46

[6] Statello L, Guo CJ, Chen LL, et al.. Gene regulation by long noncoding RNAs and its biological functions. Nat Rev Mol Cell Biol, 2021, 22(2): 96-118

[7] Park EG, Pyo SJ, Cui Y, et al.. Tumor immune microenvironment lncRNAs. Brief Bioinform, 2022, 23(1): bbab504

[8] Xue X, Yang YA, Zhang A, et al.. LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene, 2016, 35(21): 2746-2755

[9] He Y, Jiang X, Duan L, et al.. LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer by activating Wnt signaling pathway. Mol Cancer, 2021, 20(1): 156

[10] Yuan K, Lan J, Xu L, et al.. Long noncoding RNA TLNC1 promotes the growth and metastasis of liver cancer via inhibition of p53 signaling. Mol Cancer, 2022, 21(1): 105

[11] Mirzaei S, Paskeh MDA, Okina E, et al.. Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention. J Exp Clin Cancer Res, 2022, 41(1): 214

[12] Wang M, Huang T, Luo G, et al.. Long non-coding RNA MEG3 induces renal cell carcinoma cells apoptosis by activating the mitochondrial pathway. J Huazhong Univ Sci Technol Med Sci, 2015, 35(4): 541-545

[13] Lv J, Ma L, Chen X, et al.. Downregulation of LncRNAH19 and MiR-675 promotes migration and invasion of human hepatocellular carcinoma cells through AKT/GSK-3β/Cdc25A signaling pathway. J Huazhong Univ Sci Technol Med Sci, 2014, 34(3): 363-369

[14] Xia P, Li Q, Wu G, et al.. An Immune-Related lncRNA Signature to Predict Survival In Glioma Patients. Cell Mol Neurobiol, 2021, 41(2): 365-375

[15] Peng Z, Liu C, Wu M. New insights into long noncoding RNAs and their roles in glioma. Mol Cancer, 2018, 17(1): 61

[16] Mu M, Niu W, Zhang X, et al.. LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway. Oncogene, 2020, 39(45): 6879-6892

[17] Wei C, Zhang X, Peng D, et al.. LncRNA HOXA11-AS promotes glioma malignant phenotypes and reduces its sensitivity to ROS via Tpl2-MEK1/2-ERK1/2 pathway. Cell Death Dis, 2022, 13(11): 942

[18] Xia Z, Tu R, Liu F, et al.. PD-L1-related LncRNAs are associated with malignant characteristics and immune microenvironment in glioma. Aging (Albany NY), 2023, 15(19): 10785-10810

[19] Zheng J, Liu X, Wang P, et al.. Retraction Notice to: CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis. Molecular Therapy, 2022, 30(7): 2635

[20] Zhao N, Zhang J, Zhao L, et al.. Long Noncoding RNA NONHSAT079852.2 Contributes to GBM Recurrence by Functioning as a ceRNA for has-mir-10401-3p to Facilitate HSPA1A Upregulation. Front Oncol, 2021, 11: 636632

[21] Li Z, Zhu Z, Wang Y, et al.. hsa-miR-15a-5p inhibits colon cell carcinoma by targeting CCND1. Mol Med Rep, 2021, 24(4): 735

[22] Zhou X, Zhang Z, Liang X. Regulatory Network Analysis to Reveal Important miRNAs and Genes in Non-Small Cell Lung Cancer. Cell J, 2020, 21(4): 459-466

[23] Liu D, Li P, Wang X, et al.. hsa-miR-195-5p inhibits cell proliferation of human thyroid carcinoma cells via modulation of p21/cyclin D1 axis. Transl Cancer Res, 2020, 9(9): 5190-5199

[24] Luo K, Zhao Y, Liu H, et al.. Identification of Critical miRNAs as Novel Diagnostic Markers for Laryngeal Squamous Cell Carcinoma. Dis Markers, 2022, 2022: 6858411

[25] Chen S, Han M, Chen W, et al.. KIF1B promotes glioma migration and invasion via cell surface localization of MT1-MMP. Oncol Rep, 2016, 35(2): 971-977

[26] Guan Y, Yang W, Zhang F, et al.. CircPOSTN competes with KIF1B for miR-185-5p binding sites to promote the tumorigenesis of glioma. Brain Res Bull, 2022, 180: 86-96

[27] Wang L, Wang J, Jin T, et al.. FoxG1 facilitates proliferation and inhibits differentiation by downregulating FoxO/Smad signaling in glioblastoma. Biochem Biophys Res Commun, 2018, 504(1): 46-53

[28] Vengoji R, Macha MA, Nimmakayala RK, et al.. Afatinib and Temozolomide combination inhibits tumorigenesis by targeting EGFRvIII-cMet signaling in glioblastoma cells. J Exp Clin Cancer Res, 2019, 38(1): 266

[29] Sun J, He D, Fu Y, et al.. A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity. J Exp Clin Cancer Res, 2021, 40(1): 187

[30] Wpych D, Pomorski P. Calcium Signaling in Glioma Cells: The Role of Nucleotide Receptors. Adv Exp Med Bio, 2020, 1202: 67-86

[31] Hanniford D, Ulloa-Morales A, Karz A, et al.. Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis. Cancer Cell, 2020, 37(1): 55-70.e15

[32] Luo T, Yan L, Liu H. LINC00632 inhibits the malignant development of non-small cell lung cancer by downregulating miR-1203. J BUON, 2020, 25(3): 1517-1524

RIGHTS & PERMISSIONS

Huazhong University of Science and Technology