UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Li, Zhuoshi; Zhao, Kaihui; Zhou, Naichun; Liu, Feng; Xie, Fei; Yu, Shunli; Feng, Yongjie; Chen, Long; Yang, Jinjian; Tian, Fang; Jiang, Guosong

doi:10.1038/s41419-020-02935-7

Cited by 15 publications

(8 citation statements)

References 73 publications

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“…Similar to our results, previous studies have confirmed that POIR acts as a sponge of miR-182-5p (Wang et al, 2016). MiR-182-5p is reported to function as a putative oncogenic or tumor-suppressive factor and plays a role in various cancers (Gu et al, 2020;Li et al, 2020b;Yan et al, 2020). In this study, we found that miR-182-5p overexpression resulted in the sensitization of HCC cells to sorafenib, whereas miR-182 inhibition led to elevated sorafenib resistance of HCC cells.…”

Section: Discussionsupporting

confidence: 92%

LncRNA-POIR knockdown promotes hepatocellular carcinoma sensitivity to sorafenib through upregulating miR-182-5p and inhibiting autophagy

Xu¹,

Ge²,

Chen³

et al. 2022

Biocell

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Although sorafenib has been found to prolong the survival time of patients with hepatocellular carcinoma (HCC), sorafenib resistance remains an important challenge. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) contribute to drug resistance in a wide number of cancers. Human periodontal ligament stem cell (PDLSC) osteogenesis impairment-related lncRNA (POIR) is a recently defined lncRNA for which little is known regarding its function. Our study aimed to reveal the role of POIR in the development of HCC cell sorafenib resistance. The level of POIR expression in patients and tumor cells was examined by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. CCK-8, EdU, and flow cytometry assay were adopted to examine cell viability, proliferation, and apoptosis, respectively. The autophagy-associated protein expressions were determined by western blotting and autophagic flux analysis. The results of this study exhibited increased POIR in HCC tissues and cells and may be correlated with sorafenib resistance. Knockdown of POIR elevated sorafenib sensitivity by suppressing autophagy in HCC cells. Mechanically, POIR knockdown upregulated miR-182-5p, implying that miR-182-5p mediates POIR regulation.MiR-182-5p overexpression significantly enhanced chemosensitivity to sorafenib, whereas miR-182-5p inhibition had the opposite effect. The sensitization of POIR siRNA to sorafenib was abolished by co-transfection with miR-182-5p inhibitor.Our findings provide a potential target for further clinical treatment of sorafenib-resistant HCC patients.

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Section: Discussionsupporting

confidence: 92%

LncRNA-POIR knockdown promotes hepatocellular carcinoma sensitivity to sorafenib through upregulating miR-182-5p and inhibiting autophagy

Xu¹,

Ge²,

Chen³

et al. 2022

Biocell

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“…MiRNA is an important post-transcriptional regulator, resulting in a decrease in mRNA expression through direct base pairing with mRNA 3′-UTR target sites [ 30 ]. MiR-182-5p has been proven to regulate the key process in multiple cancers, such as breast cancer, bladder cancer, and colon cancer [ [31] , [32] , [33] , [34] ], but our study is the first to demonstrate its acting as a functional target in the ceRNA network in adipocytes and cachexia.…”

Section: Discussionmentioning

confidence: 78%

Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia

Ding

Sun

Han

et al. 2021

Molecular Metabolism

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Objective Cancer-associated cachexia is a devastating pathological disorder characterized by skeletal muscle wasting and fat storage depletion. Circular RNA, a newly discovered class of noncoding RNAs with important roles in regulating lipid metabolism, has not been fully understood in the pathology of cachexia. We aimed to identify circular RNAs that are upregulated in adipose tissues from cachectic patients and explore their function and mechanism in lipid metabolism. Methods Whole transcriptome RNA sequencing was used to screen for differentially expressed circRNAs. Quantitative reverse transcription PCR was applied to detect the expression level of circPTK2 in adipose tissues. The diagnostic value of circPTK2 was evaluated in adipose tissues from patients with and without cachexia. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circPTK2 on lipolysis and adipogenesis. Mechanistically, luciferase reporter assay, RNA immunoprecipitation, and fluorescent in situ hybridization were performed to confirm the interaction between circPTK2 and miR-182-5p in adipocytes. Results We detected 66 differentially expressed circular RNA candidates and proved that circPTK2 was upregulated in adipose tissues from cachectic patients. Then we identified that circPTK2 was closely related to the pathological process of cachexia and could be used as a diagnostic marker. Mechanistically, circPTK2 bound competitively to miR-182-5p and abrogated the suppression on its target gene JAZF1, which finally led to promotion of lipolysis and inhibition of adipogenesis. In vivo experiments demonstrated that overexpression of circPTK2 inhibited adipogenesis and enhanced lipolysis. Conclusions Our findings reveal the novel role of circPTK2 in promoting lipolysis and reducing adipogenesis via a ceRNA mechanism and provide a potential diagnostic biomarker and therapeutic target for cancer-associated cachexia.

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“…RNF5, a member of E3 ubiquitin protein ligase, exerts the neuroprotection effect as a downstream molecular of the DJ-1/Akt signaling pathway (Zhang et al, 2012). UBAC2, which serves as a regulator of ER-associated protein degradation, plays a critical role in promoting the occurrence and development of malignant tumors (Gu et al, 2020). It has been reported that the mutation of DNAJC protein family may contribute to Parkinson's disease pathogenesis, suggesting that they may be considered as effective therapeutic targets in neurodegenerative diseases (Roosen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Identification of endoplasmic reticulum stress-associated genes and subtypes for prediction of Alzheimer’s disease based on interpretable machine learning

Lai

Lin

et al. 2022

Front. Pharmacol.

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Introduction: Alzheimer’s disease (AD) is a severe dementia with clinical and pathological heterogeneity. Our study was aim to explore the roles of endoplasmic reticulum (ER) stress-related genes in AD patients based on interpretable machine learning.Methods: Microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. We performed nine machine learning algorithms including AdaBoost, Logistic Regression, Light Gradient Boosting (LightGBM), Decision Tree (DT), eXtreme Gradient Boosting (XGBoost), Random Forest, K-nearest neighbors (KNN), Naïve Bayes, and support vector machines (SVM) to screen ER stress-related feature genes and estimate their efficiency of these genes for early diagnosis of AD. ROC curves were performed to evaluate model performance. Shapley additive explanation (SHAP) was applied for interpreting the results of these models. AD patients were classified using a consensus clustering algorithm. Immune infiltration and functional enrichment analysis were performed via CIBERSORT and GSVA, respectively. CMap analysis was utilized to identify subtype-specific small-molecule compounds.Results: Higher levels of immune infiltration were found in AD individuals and were markedly linked to deregulated ER stress-related genes. The SVM model exhibited the highest AUC (0.879), accuracy (0.808), recall (0.773), and precision (0.809). Six characteristic genes (RNF5, UBAC2, DNAJC10, RNF103, DDX3X, and NGLY1) were determined, which enable to precisely predict AD progression. The SHAP plots illustrated how a feature gene influence the output of the SVM prediction model. Patients with AD could obtain clinical benefits from the feature gene-based nomogram. Two ER stress-related subtypes were defined in AD, subtype2 exhibited elevated immune infiltration levels and immune score, as well as higher expression of immune checkpoint. We finally identified several subtype-specific small-molecule compounds.Conclusion: Our study provides new insights into the role of ER stress in AD heterogeneity and the development of novel targets for individualized treatment in patients with AD.

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UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Cited by 15 publications

References 73 publications

LncRNA-POIR knockdown promotes hepatocellular carcinoma sensitivity to sorafenib through upregulating miR-182-5p and inhibiting autophagy

LncRNA-POIR knockdown promotes hepatocellular carcinoma sensitivity to sorafenib through upregulating miR-182-5p and inhibiting autophagy

Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia

Identification of endoplasmic reticulum stress-associated genes and subtypes for prediction of Alzheimer’s disease based on interpretable machine learning

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