Glycogen Phosphorylase B Is Regulated by miR101-3p and Promotes Hepatocellular Carcinoma Tumorigenesis

Cui, Guangying; Wang, Huifen; Liu, Wenli; Xing, Jiyuan; Song, Wengang; Zeng, Zhaohai; Liu, Liwen; Wang, Hai‐Yu; Wang, Xuemei; Luo, Hong; Leng, Xiaoyang; Shen, Shen

doi:10.3389/fcell.2020.566494

Cited by 18 publications

(13 citation statements)

References 41 publications

(65 reference statements)

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“…miR-101 is a downregulated miRNA in HCC tissues and its expression was negatively associated with a poor prognosis of HCC patients ( 29 ). By targeting several oncogenes, such as Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2), Dual-specificity phosphatase (DUSP), Myeloid cell leukemia-1 (Mcl-1), miR-101 exerts as a tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: CCDC88A Post-Transcriptionally Regulates VEGF via miR-101 and Subsequently Regulates Hepatocellular Carcinoma

Chen

et al. 2022

Front. Immunol.

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BackgroundmiR-101 is one of the most abundantly expressed microRNA (miRNA) and exerst a critical role in hepatocellular carcinoma (HCC) by targeting to 3’ -untranslated region (UTR) of Girders of actin filaments (CCDC88A) and Vascular endothelial growth factor (VEGF) mRNA, but the underlying molecular mechanism remains to be elucidated. This study aimed to investigate the potential role of CCDC88A on malignancies and stemness by regulating VEGF via miR-101 in HCC.MethodsGene Expression Profiling Interactive Analysis (GEPIA) was employed to analyze the relevance of CCDC88A expression with prognosis in HCC. Tissue slides were performed to confirm the protein level of CCDC88A in HCC. Correlation between CCDC88A and VEGF was transcriptionally and post-transcriptionally detected, followed by evaluation of malignancies.ResultsBy employing Immunohistochemistry, we found CCDC88A protein was upregulated in HCC tissues, which is closely correlated to poor prognosis and survival rate. Employment of GEPIA revealed the positive correlation between CCDC88A and VEGF in HCC, but not in liver tissue. Silencing of CCDC88A in Huh-7 and SK-HEP-1 cells significantly decreased proliferation, cell cycle phases, migration, invasion, colony formation, and tumor formation. Introduction of miR-101 mimics specifically targeting CCDC88A and VEGF decreased protein levels of both CCDC88A and VEGFA. Notably, inhibition of miR-101 reversed the correlation between CCDC88A and VEGFA protein levels, indicating that CCDC88A and VEGF may exert as a miR-101 sponge. The addition of SKLB1002, a VEGFR2 inhibitor inhibited malignant behaviors, which was further inhibited by the introduction of miR-101 mimics, indicating that CCDC88A regulates malignant behaviors partially via regulating VEGF. Moreover, CCDC88A also promotes the stemness of cancer stem-like cells derived from HCC cells depending on VEGF modification.ConclusionTaken together, our findings suggested that the miR-101/CCDC88A/VEGF axis could be a potential therapeutic target of HCC treatment.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: CCDC88A Post-Transcriptionally Regulates VEGF via miR-101 and Subsequently Regulates Hepatocellular Carcinoma

Chen

et al. 2022

Front. Immunol.

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“…MiR-101-3p induced M1 to M2 macrophage-type conversion and enhanced cell migration of breast and ovarian ( Zhao et al, 2021 ). MiR-101-3p promoted hepatocellular carcinoma carcinogenesis by targeting glycogen phosphorylase B ( Cui et al, 2020 ). Li et al (2019) reported that miR-101-3p targeted TRIM44 to inhibit EMT and suppress glioblastoma cell proliferation metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway

Guo

Chen

Cao

et al. 2021

Front. Cell Dev. Biol.

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Cancer-associated fibroblasts (CAFs) are major component of tumor microenvironment (TME), which plays crucial roles in tumor growth, invasion and metastasis; however, the underling mechanism is not fully elucidated. Despite many studies are focused on the tumor promoting effect of CAFs-derived cytokines, the upstream regulators of cytokine release in CAFs is largely unknown. Here we found that miR-101-3p was downregulated in primary lung cancer-associated CAFs compared to normal fibroblasts (NFs). Ectopic overexpression of miR-101-3p suppressed CAFs activation, and abrogated the promoting effect of CAFs on migration and invasion of non-small cell lung cancer cells (NSCLC), through attenuating CAFs’ effect on epithelial mesenchymal transition (EMT) process, metastasis-related genes (MMP9, TWIST1) and AKT/endothelial nitric oxide synthase (eNOS) signaling pathway. Further study indicated that vascular endothelial growth factor A (VEGFA) was a novel target of miR-101-3p, and CAFs-derived VEGFA mediated the effect of miR-101-3p on migration and invasion of lung cancer cells, demonstrated by using recombinant VEGFA and VEGFA neutralizing antibody. Interestingly, the analysis of the Cancer Genome Atlas (TCGA) database revealed that lung cancer tissues expressed lower level of miR-101-3p than non-cancerous tissues, and low/medium-expression of miR-101-3p was associated with poor overall survival (OS) rate. Moreover, the mouse xenograft experiment also showed that CAFs accelerated tumor growth whereas miR-101-3p diminished CAFs’ effect. These findings revealed a novel mechanism that CAFs facilitated lung cancer metastasis potential via miR-101-3p/VEGFA/AKT signaling pathway, suggesting miR-101-3p as a potential candidate for metastasis therapy.

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“…The glycogen metabolism plays a key role in tumorigenesis. Not only PYGM, but also PYGB level is up-regulated in different kinds of cancer such as colorectal cancer [ 69 ], hepatocellular carcinoma [ 70 ], prostate cancer [ 71 ], non-small cell lung cancer (NSCLC) [ 72 ], and ovarian cancer [ 73 ]. However, one should keep in mind that carcinogenesis is a complex process in which many factors interact together [ 74 ].…”

Section: The Biological Importance Of Pygmmentioning

confidence: 99%

Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

Migocka-Patrzałek

Elías

2021

Cells

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Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. However, it is expressed in tissues other than muscle, such as the brain, lymphoid tissues, and blood. PYGM is important not only in glycogen metabolism, but also in such diverse processes as the insulin and glucagon signaling pathway, insulin resistance, necroptosis, immune response, and phototransduction. PYGM is implicated in several pathological states, such as muscle glycogen phosphorylase deficiency (McArdle disease), schizophrenia, and cancer. Here we attempt to analyze the available data regarding the protein partners of PYGM to shed light on its possible interactions and functions. We also underline the potential for zebrafish to become a convenient and applicable model to study PYGM functions, especially because of its unique features that can complement data obtained from other approaches.

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Glycogen Phosphorylase B Is Regulated by miR101-3p and Promotes Hepatocellular Carcinoma Tumorigenesis

Cited by 18 publications

References 41 publications

RETRACTED: CCDC88A Post-Transcriptionally Regulates VEGF via miR-101 and Subsequently Regulates Hepatocellular Carcinoma

RETRACTED: CCDC88A Post-Transcriptionally Regulates VEGF via miR-101 and Subsequently Regulates Hepatocellular Carcinoma

Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway

Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

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