Silencing of HAS2‐AS1 mediates PI3K/AKT signaling pathway to inhibit cell proliferation, migration, and invasion in glioma

Zhao, Zhenying; Liang, Tian; Feng, Shijun

doi:10.1002/jcb.28430

Cited by 16 publications

(10 citation statements)

References 23 publications

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“…Recent studies have demonstrated the possible potential molecular pathways for SPHK1 and HAS2 in cancer progression, one of which is that SPHK1 induces lung cancer cell migration and paclitaxel resistance by modulating IGF-1-induced EMT [ 27 ]. HAS2 mediated hyaluronan production through Notch1 activation and liver fibrosis [ 28 , 29 ]. The GO and KEGG results showed that the coregulated genes mainly involved in cell invasion, cell adhesion, and positive regulation of angiogenesis by ECM-receptor interaction, focal adhesion, and PI3K-AKT signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

Zhang

Wang³

et al. 2021

BioMed Research International

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Objective. SPHK1 and HAS2 have been reported to play important roles in tumorigenesis and development. However, their expression and prognostic value in pancreatic cancer (PC) remain unclear. This study is aimed at investigating the expression of SPHK1 and HAS2 on the prognosis of pancreatic cancer. Materials and Methods. The expression of SPHK1 and HAS2 in pancreatic cancer tissues was analyzed through TCGA and GTEx databases and validated by qRT-PCR and Western blot in pancreatic cancer cell lines. χ 2 test was used to explore the correlation of the SPHK1 and HAS2 expressions with clinical characteristics. Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic and diagnostic roles of SPHK1 and HAS2 in pancreatic cancer. Additionally, Spearman correlation analysis was applied to assess the correlation between the SPHK1 and HAS2 in pancreatic cancer. GO analysis and KEGG analysis were applied to explore the possible signaling pathway that SPHK1 and HAS2 coregulated genes mediated. Results. The expression of SPHK1 and HAS2 was markedly upregulated in pancreatic cancer tissue and cell lines, respectively. Furthermore, there was a significant positive correlation between SPHK1 and HAS2 expressions. ROC curves showed that SPHK1 combine with HAS2 has good diagnostic value in pancreatic cancer patients with 85% sensitivity and 99.4% specificity. Kaplan-Meier analysis showed that increased expression of SPHK1 and HAS2 was significantly associated with short overall survival (OS) of pancreatic cancer patients. GO and KEGG results revealed that SPHK1 and HAS2 mainly involved cell proliferation and invasion mediated by extracellular matrix- (ECM-) receptor interaction, focal adhesion, and PI3K-AKT signaling pathways. Conclusions. Overexpression of SPHK1 and HAS2 could be important markers for the prognosis of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

Zhang

Wang³

et al. 2021

BioMed Research International

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“…HA degradation has been explored as a therapeutic target in several studies ( 68 , 76 , 77 , 117 , 221 , 222 ). Clinical trials have shown that treatment with HYAL as adjuvant chemotherapy improves drug biodistribution and particularly access to the tumor site, contributing to clinically relevant remissions in high-grade astrocytomas and to the efficacy of chemotherapy in pediatric brain tumors ( 223 , 224 , 225 ).…”

Section: Hyaluronan As a Therapeutic Target In Glioblastomamentioning

confidence: 99%

The scrambled story between hyaluronan and glioblastoma

Pibuel

Poodts

Díaz

et al. 2021

Journal of Biological Chemistry

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Advances in cancer biology are revealing the importance of the cancer cell microenvironment on tumorigenesis and cancer progression. Hyaluronan (HA), the main glycosaminoglycan in the extracellular matrix, has been associated with the progression of glioblastoma (GBM), the most frequent and lethal primary tumor in the central nervous system, for several decades. However, the mechanisms by which HA impacts GBM properties and processes have been difficult to elucidate. In this review, we provide a comprehensive assessment of the current knowledge on HA’s effects on GBM biology, introducing its primary receptors CD44 and RHAMM and the plethora of relevant downstream signaling pathways that can scramble efforts to directly link HA activity to biological outcomes. We consider the complexities of studying an extracellular polymer and the different strategies used to try to capture its function, including 2D and 3D in vitro studies, patient samples, and in vivo models. Given that HA affects not only migration and invasion, but also cell proliferation, adherence, and chemoresistance, we highlight the potential role of HA as a therapeutic target. Finally, we review the different existing approaches to diminish its protumor effects, such as the use of 4-methylumbelliferone, HA oligomers, and hyaluronidases and encourage further research along these lines in order to improve the survival and quality of life of GBM patients.

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“…Multiple studies have reported that HAS2-AS1 is involved in the regulatory mechanism of ceRNA network and modulates the proliferation and migration of tumor cells [13,18]. Here, HAS2-AS1 was chosen for follow-up experiments.…”

Section: Silencing Has2-as1 Inhibits Glioma Cell Invasion and Migrationmentioning

confidence: 99%

“…Related studies have found that HAS2-AS1 is abnormally expressed in a variety of cancers, such as epithelial ovarian cancer [9], breast cancer [10], non-small cell lung cancer [11] and oral squamous cell cancer [12], and induces the development of cancers. Silencing of HAS2-AS1 mediates PI3K/Akt signaling pathway to inhibit cell proliferation, migration, and invasion of glioma [13]. However, the mechanism of the high expression of HAS2-AS1 in glioma is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

You

et al. 2020

Bioscience Reports

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Objective: The role of lncRNAs in tumor has been widely concerned. This study took HAS2-AS1 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 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 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 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 upregulation of lncRNA HAS2-AS1 and promoted glioma cell invasion and migration.

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Silencing of HAS2‐AS1 mediates PI3K/AKT signaling pathway to inhibit cell proliferation, migration, and invasion in glioma

Cited by 16 publications

References 23 publications

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

The scrambled story between hyaluronan and glioblastoma

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

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