Epigenetic silencing of ALX4 regulates microcystin-LR induced hepatocellular carcinoma through the P53 pathway

Zhao, Ji; Chen, Hongqiang; Yang, Huifang; Li, Yan; Chen, Dong-jiao; Huang, Yujing; He, Liang-Ying; Zheng, Chuanfen; Wang, Lingqiao; Wang, Jia; Zhang, Na; Cao, Jia; Liu, Jinyi; Shu, Weiqun; Liu, Wenbin

doi:10.1016/j.scitotenv.2019.05.144

Cited by 22 publications

(6 citation statements)

References 36 publications

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“…These lncRNAs were primarily associated with tumor grade, TNM stage, and lymphatic metastasis in HCC. Among these 26 lncRNAs, MCM3AP-AS1, UCA1, AKR7L, C3P1, AKR1C6P, LINC01018, and A1BG-AS1 have been reported in lymphatic metastasis and invasion and are diagnostic biomarkers for HCC (Praml, Savelyeva & Schwab, 2003;Wang et al, 2006;Zhang, Luo & Zhang, 2019;Zhao et al, 2019a;Zhao et al, 2019b;Zhao et al, 2019c;Zheng et al, 2015). However, other lncRNAs are not yet associated with HCC progression.…”

Section: Discussionmentioning

confidence: 99%

“…6B). The MAPK signaling pathway has been shown to participate in the progression of HCC (Zhao et al, 2018), and the P53 signaling pathway is a key pathway in HCC cell proliferation and apoptosis (Zhao et al, 2019b). Bladder cancer, small cell lung cancer, pathways in cancer, and the PI3K-AKT signaling pathway may also be involved in the regulation of cancer progression (Tang et al, 2019).…”

Section: Function Analysis Of Intersected Mrnasmentioning

confidence: 99%

“…Closely related dysregulated lncRNAs may assist in identifying valuable biomarkers for the diagnosis and prognosis of HCC. Current studies of HCC and lncRNAs have mainly focused on sequencing small tissue samples and cell lines (Tan et al, 2019;Zhao et al, 2019a;Zhao et al, 2019b;Zhao et al, 2019c). Large sample population studies are rarely reported.…”

Section: Introductionmentioning

confidence: 99%

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Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma

Zhang

Yang

et al. 2020

PeerJ

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Background Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis and a high incidence. The molecular changes and novel biomarkers of HCC need to be identified to improve the diagnosis and prognosis of this disease. We investigated the current research concentrations of HCC and identified the transcriptomics-related biomarkers of HCC from The Cancer Genome Atlas (TGCA) database. Methods We investigated the current research concentrations of HCC using literature metrology analysis for studies conducted from 2008 to 2018. We identified long noncoding RNAs (lncRNAs) that correlated with the clinical features and survival prognoses of HCC from The Cancer Genome Atlas (TGCA) database. Differentially expressed genes (lncRNAs, miRNAs, and mRNAs) were also identified by TCGA datasets in HCC tumor tissues. A lncRNA competitive endogenous RNA (ceRNA) network was constructed from lncRNAs based on intersected lncRNAs. Survival times and the association between the expression levels of the key lncRNAs of the ceRNA network and the clinicopathological characteristics of HCC patients were analyzed using TCGA. Real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the results in tissue samples from 20 newly-diagnosed HCC patients. Results Analysis of the literature pertaining to HCC research revealed that current research is focused on lncRNA functions in tumorigenesis and tumor development. A total of 128 HCC dysregulated lncRNAs were identified; 66 were included in the co-expressed ceRNA network. We analyzed survival times and the associations between the expression of 66 key lncRNAs and the clinicopathological features of the HCC patients identified from TCGA. Twenty-six lncRNAs were associated with clinical features of HCC (P < 0.05) and six key lncRNAs were associated with survival time (log-rank test P < 0.05). Six key lncRNAs were selected for the validation of their expression levels in 20 patients with newly diagnosed HCC using qRT-PCR. Consistent fold changes in the trends of up and down regulation between qRT-PCR validation and TCGA proved the reliability of our bioinformatics analysis. Conclusions We used integrative bioinformatics analysis of the TCGA datasets to improve our understanding of the regulatory mechanisms involved with the functional features of lncRNAs in HCC. The results revealed that lncRNAs are potential diagnostic and prognostic biomarkers of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Function Analysis Of Intersected Mrnasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma

Zhang

Yang

et al. 2020

PeerJ

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“…CUL4A participates in the proteolysis of p53, and CUL4A depletion results from an accumulation of p53 (13). p53 is a tumor suppressor gene, which is involved in the growth and metastasis of various types of cancer (30)(31)(32). CSN6, a pivotal subunit of the constitutive COP9 CSN, is notably upregulated in a number of different types of human cancer (33,34).…”

Section: Discussionmentioning

confidence: 99%

CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6

Wang¹,

Chen

2020

Mol Med Rep

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Endometrial cancer (EC) is a common malignant gynecological tumor arising from the endometrium, with an annually increasing morbidity and mortality. The present study aimed to investigate the functions of cullin 4A (CUL4A) in EC, as well as the underlying mechanisms. CUL4A expression was assessed in several human EC cells and normal human endometrial epithelial cells (hEECs) via reverse transcription-quantitative polymerase chain reaction and western blotting. Subsequently, short hairpin (sh) RNA-CULA4 was transfected into cells, and cell proliferation, invasion and migration were detected using Cell Counting kit-8, Transwell and wound healing assays, respectively. The STRING database identified that CSN6 interacted with CULA4, and immunoprecipitation was performed to verify the interaction. Subsequently, following CUL4A knockdown, pcDNA3.1-CSN6 was transfected into cells and its effects on cell proliferation, invasion and migration were assessed. The expression levels of matrix metallopeptidase (MMP)2, MMP9 and p53 were evaluated via western blotting. The results indicated that CUL4A was highly expressed in EC cells, compared with hEECs. CULA4-knockdown notably inhibited EC cell proliferation, invasion and migration. The expression levels of MMP2 and MMP9 were significantly decreased, while p53 expression was enhanced following CUL4A-knockdown. The immunoprecipitation assay verified that COP9 signalosome subunit 6 (CSN6) interacted with CULA4. Furthermore, CSN6-overexpression alleviated the inhibitory effects of CUL4A-knockdown on EC cell proliferation, invasion and migration. Similarly, CSN6 overexpression reversed CUL4A-knockdown-mediated effects on the expression of MMP2, MMP9 and p53. In summary, the results demonstrated that CUL4A regulated EC cell proliferation, invasion and migration by interacting with CSN6.

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“…In contrast, tumor suppressive circRNAs impede HCC glycolysis. For example, aristaless-like homeobox 4 (ALX4) inhibits HCC proliferation and invasion[ 80 ], and circ_0001445, a tumor suppressor, enhances ALX4 expression by sponging miR-942-5p, thus inhibiting HCC glycolysis[ 81 ]. Collectively, circRNAs have become important regulatory factors in glycolysis in HCC cells, but the specific mechanism of their regulation of metabolism remains to be elucidated.…”

Section: Role Of Circrnas In Hccmentioning

confidence: 99%

Circular RNAs in hepatocellular carcinoma: Recent advances

Niu¹,

Wang²

2022

WJGO

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Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.

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Epigenetic silencing of ALX4 regulates microcystin-LR induced hepatocellular carcinoma through the P53 pathway

Cited by 22 publications

References 36 publications

Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma

Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma

CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6

Circular RNAs in hepatocellular carcinoma: Recent advances

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