Circular RNA UBR1 promotes the proliferation, migration, and invasion but represses apoptosis of lung cancer cells via modulating microRNA-545-5p/SSFA2 axis

Su, Peng; Mao, Feng; Zhang, Jian; Zhang, Hui; Wang, Ming-Bo; Xu, Yong; Tian, Ziqiang

doi:10.1080/21655979.2021.2004977

Cited by 12 publications

(5 citation statements)

References 48 publications

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“…First, UBR1 was found to be overexpressed in various types of cancers, particularly GC, which is in agreement with the results of previous studies. Previous research has also shown increased expression of cyclic UBR1 in breast [22] and lung [23] cancers. Our study using BioSign predicted that high expression of UBR1 in GC correlates with unfavorable pathological features and poor prognosis.…”

Section: Discussionmentioning

confidence: 70%

UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer

Wang¹,

Han²,

Wu³

et al. 2023

Preprint

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Background Ubiquitination is a targeted protein modification process mediated by intracellular molecules. UBR1 encodes a protein that binds to unstable N-terminal residues of substrate proteins and contributes to the formation of substrate-linked polyubiquitin chains. However, the cellular pathways and the function of UBR1 in tumors have received inadequate attention. Therefore, the aim of this study is to examine the potential of UBR1 as a prognostic biomarker and immunotherapy target for stomach adenocarcinoma (STAD) as well as its biological function and molecular mechanism in relation to the disease. Methods Differential expression and pan-cancer GSEA analyses were performed using TCGA, GEO and GTEx datasets. Immunohistochemical differences between cancer and paraneoplastic tissues were analyzed using the HPA database to identify pathways enriched by UBR1 in AGS cells. Besides, with the help of Kaplan-Meier curves, univariate and multivariate Cox regression, and receiver operating characteristic (ROC) curve studies, the prognostic and diagnostic roles of UBR1 can be identified and determined. The correlation between UBR1 expression and clinical parameters was predicted by using the TCGA and GEO databases. The UBR1 mutation data were retrieved from the cBioPortal database. The biological mechanisms of UBR1 were investigated using GO and KEGG enrichment analyses. TIMER and EPIC computational methods were utilized to establish the connection between UBR1 and immune infiltration. Protein expression was determined using immunohistochemistry (IHC) and Western blot analysis (WB). In regard to mRNA expression, Quantitative Real-time PCR (qRT-PCR), it was analyzed by taking advantage of Quantitative Real-time PCR (qRT-PCR). Quantitative Immunoprecipitation (IP) assays were used to detect protein-protein interactions. Cell proliferation was evaluated using CCK8 and colony formation assays. Cell invasion was determined using wound healing assays and Transwell. Apoptosis was analyzed using flow cytometry. Result UBR1 was upregulated in 28 cancer types,including STAD, and its overexpression was validated in gastric cancer cell lines and tissues. UBR1 expression was associated with advanced pathological characteristics. High UBR1 expression was linked to poor prognostic outcomes, including progression-free interval (PFI), overall survival (OS), disease-specific survival (DSS), surgery, chemotherapy, and HER2 expression. UBR1 expression was significantly correlated with clinical parameters, such as age, gender, TMN stage, pathological stage, tumor resection, and anti-reflux therapy. Amplifications and deletions were the frequent genetic alterations associated with UBR1. According to the KEGG and GSEA, UBR1 was significantly associated with several cancer pathways, oxidative phosphorylation, and the TNF-NFκB pathway. UBR1 exhibited a significant correlation with immunotherapy and immune cell infiltration, and a direct interaction with CD274. Also, the proliferation and invasion of STAD cells were inhibited due to the UBR1 knockdown, but apoptosis was promoted in a contrary way. Conclusion The results of this investigation show that UBR1 is overexpressed in STAD, promoting its progression, and positively correlates with immune cell infiltration and immunotherapeutic responses. Therefore, UBR1 could be a promising biomarker in the prognosis and immunotherapy field of STAD.

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Section: Discussionmentioning

confidence: 70%

UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer

Wang¹,

Han²,

Wu³

et al. 2023

Preprint

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“… 35 Additionally, the Circ_UBR1/miR-545-5p/SSFA2 axis promoted the malignant behavior of cancer cells in LC. 36 However, the Circ_0001367/miR-545-3p/LUZP1 axis suppressed cancer progression in GBM/LGG. 4 …”

Section: Mir-545 and Its Competing Endogenous Ribonucleic Acids (Cernas)mentioning

confidence: 99%

“…miR-545-3p promotes apoptosis by targeting 10 downstream PCGs, including CCND2 in NPC 57 ; KU70 57 and HDGF 6 in LC; CBLL1, 7 PRKCA, 15 and YAP1 in NSCLC 26 ; FAM98A in EC 32 ; SLC7A11 in THCA 35 ; PFKFB3 in CRC 29 ; and PPA1 in OC. 32 miR-545-5p promotes apoptosis by targeting SSFA2 in LC 36 and MDM2 in CRC. 48 …”

Section: Mir-545 Regulates Cell Behaviorsmentioning

confidence: 99%

“…In contrast, research has shown that miR-545-3p can promote cancer cell invasion and migration by targeting three genes: LUZP1 in GBM/LGG, 4 SMAD7 in HCC, 28 and MT1M in HCC. 53 Additionally, miR-545-5p promotes cancer cell invasion and migration by targeting six genes: CCND2 in NPC, 44 SSFA2 in LC, 36 c-MET in NSCLC, 45 CNPY2 in GC, 61 MDM2 in CRC, 48 and DIMT1 in SaOS. 9 …”

Section: Mir-545 Regulates Cell Behaviorsmentioning

confidence: 99%

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Current and future perspectives on the regulation and functions of miR-545 in cancer development

Shen,

Su,

Wang

et al. 2024

Cancer Pathogenesis and Therapy

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“…Su et al . [ 8 ] demonstrated that circUBR1 enhances lung cancer cell migration and invasion via the miR-545-5p/SSFA2 axis. Additionally, other circRNAs regulate apoptosis-related protein expression.…”

Section: Introductionmentioning

confidence: 99%

CircRNA protein tyrosine phosphatase receptor type a suppresses proliferation and induces apoptosis of lung adenocarcinoma cells via regulation of microRNA-582-3p

Jiang

Yang

et al. 2022

Bioengineered

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Circular RNAs (circRNAs) are associated with cancer progression. The present study aimed to examine the function of circRNA protein tyrosine phosphatase receptor type A (circRNA_PTPRA) in lung cancer cells and elucidate the underlying molecular mechanisms. The levels of circRNA_PTPRA and microRNA (miRNA/miR)-582-3p were measured in lung cancer tissue and cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation and apoptosis were evaluated using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The expression of cyclin D1, caspase-3, and cleaved caspase-3 was assessed via western blotting. The sites of circRNA_PTPRA/miR-582-3p interaction were identified using StarBase, and validated using a dual-luciferase reporter assay. We observed that circRNA_PTPRA levels were remarkably decreased, and miR-582-3p expression was up-regulated in lung cancer tissues and cells. circRNA_PTPRA directly interacts with miR-582-3p and downregulates miR-582-3p expression in lung cancer cells. Moreover, an miR-582-3p inhibitor decreased lung cancer cell proliferation and promoted apoptosis. The overexpression of circRNA_PTPRA decreased cell proliferation and increased apoptotic cell numbers, whereas miR-582-3p overexpression reversed these effects. These findings demonstrate that the up-regulation of circRNA_PTPRA significantly reduces lung cancer cell proliferation and induces apoptosis by regulating miR-582-3p expression.

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Circular RNA UBR1 promotes the proliferation, migration, and invasion but represses apoptosis of lung cancer cells via modulating microRNA-545-5p/SSFA2 axis

Cited by 12 publications

References 48 publications

UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer

UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer

Current and future perspectives on the regulation and functions of miR-545 in cancer development

CircRNA protein tyrosine phosphatase receptor type a suppresses proliferation and induces apoptosis of lung adenocarcinoma cells via regulation of microRNA-582-3p

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