LncRNA GAS5 represses stemness and malignancy of gliomas via elevating the SPACA6-miR-125a/let-7e Axis

Wu, Shuang; Ren, Kaixi; Zhao, Jing; Li, Juan; Jia, Bo; Wu, Xiaohu; Dou, Yanan; Fei, Xiaowei; Yu, Huan; He, Xin; Wang, Tingting; Lv, Weihao; Wang, Li; Wang, Yangang; Zhao, Junlong; Zhou, Fei; Li, Sanzhong

doi:10.3389/fonc.2022.803652

Cited by 7 publications

(4 citation statements)

References 58 publications

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“…GAS5 has been widely considered as a potential cancer suppressor gene, with its downregulation associated with cancer in multiple different tissues[ 41 - 43 ]. In our study, however, we discovered that GAS5 was overexpressed in HCC tumor tissues, and its overexpression led to a poor prognosis of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

Pan,

Zhang,

Wang

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

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Section: Discussionmentioning

confidence: 99%

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

Pan,

Zhang,

Wang

et al. 2024

World J Gastrointest Oncol

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“…It was shown that miR-125a controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis [25]. For miR-let-7e, previous studies have shown that JARID1B demethylase promotes tumor cell proliferation by epigenetically inhibiting the tumor suppressor miR-let-7e [26].…”

Section: Discussionmentioning

confidence: 99%

miR-99b/let-7e/miR-125a cluster suppresses pancreatic cancer through regulation of NR6A1

2024

Am J Cancer Res

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This experiment investigates how the miR-99b/let-7e/miR-125a cluster regulates the mechanism of NR6A1 involved in the invasive and metastatic effects of pancreatic cancer (PCa). Bioinformatics prediction and dual luciferase reporter gene assay were applied to verify the targeted relationship between miR-99b/let-7e/miR-125a and NR6A1. ASPC1 cells underwent transfection with lentiviruses to overexpress miR-99b/let-7e/miR-125a (individual or together) to explore functions of miR-99b/let-7e/miR-125a cluster governing NR6A1 in PCa. The detection of tumorigenesis was verified by tumor formation assay in nude mice in vivo, and mouse models of liver metastasis of PCa observed cell metastasis of PCa. MiR-99b/let-7e/miR-125a cluster was screened for differential expression in PCa. NR6A1 was confirmed as a target gene of the miR-99b/let-7e/miR-125a cluster. Findings demonstrated that overexpression of the miR-99b/let-7e/miR-125a cluster inhibited cell invasion, metastasis, proliferation, and tumorigenesis in PCa. Conversely, overexpressed NR6A1, a crucial gene in the miR-99b/let-7e/miR-125a cluster, promoted cell invasion, migration, and proliferation in PCa. Moreover, the overexpression of the miR-99b/ let-7e/miR-125a cluster inhibited liver metastases and tumor formation. Thus, the study concludes that the miR-99b/let-7e/miR-125a cluster impedes the invasion and metastasis of PCa cells via targeting the NR6A1 gene.

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“…The tumour suppression of GAS5 has been associated with gliomas, and the expression level of this lncRNA correlates with the degree of tumour malignancy and patient survival time. GAS5 transcription is higher in lower-grade gliomas compared to higher-grade gliomas, including GBM [279]. Low levels of GAS5 expression observed in GBM compared to healthy controls correlate with poor prognosis [269].…”

Section: Emerging Lncrna Biomarkers Of Gbmmentioning

confidence: 96%

lncRNA Biomarkers of Glioblastoma Multiforme

Pokorná,

Černá,

Boussios

et al. 2024

Biomedicines

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Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients’ blood.

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LncRNA GAS5 represses stemness and malignancy of gliomas via elevating the SPACA6-miR-125a/let-7e Axis

Cited by 7 publications

References 58 publications

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

miR-99b/let-7e/miR-125a cluster suppresses pancreatic cancer through regulation of NR6A1

lncRNA Biomarkers of Glioblastoma Multiforme

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