&lt;p&gt;Long Noncoding RNA PCAT18 Upregulates SPRR3 to Promote Colorectal Cancer Progression by Binding to miR-759&lt;/p&gt;

Background Much attention has been paid to the regulatory role of microRNA (miRNA) in insulin resistance. Nevertheless, how miR-140-5p regulates insulin resistance remains unclear. In this research, we aim to investigate the roles of miR-140-5p in insulin resistance. Methods qRT-PCR is used to analyze the expression level of miR-140-5p in insulin-resistant HepG2 cells. Glucose consumption and glucose uptake are detected to study the effect of miR-140-5p knockdown in insulin-resistant HepG2 cells and miR-140-5p overexpression in HepG2 cells. Bioinformatic analysis, luciferase reporter assay and confirmatory experiments are applied to identify the target gene bound with miR-140-5p and study the effect of miR-140-5p on the downstream substrates of target genes. Rescue experiments have verified the roles of miR-140-5p and target gene in glucose metabolism. Results The expression level of miR-140-5p was upregulated in insulin-resistant HepG2 cells and was significantly correlated with cellular glucose metabolism. Functionally, miR-140-5p overexpression induced impairment of glucose consumption and glucose uptake. Besides, bioinformatics analysis indicated that glycogen synthetase (GYS1) and protein phosphatase 1 catalytic subunit gamma (PPP1CC) were the target genes of miR-140-5p. Western blotting and qRT-PCR results revealed a negative correlation between GYS1, PPP1CC and miR-140-5p. The glycogen detection results showed that miR140-5p inhibited the production of the downstream substrates of the target gene. Rescue experiments showed that inhibition of GYS1 or PPP1CC partially enhanced the insulin-resistant effects of miR-140-5p knockdown in insulin-resistant HepG2 cells. Conclusion miR-140-5p overexpression augments the development of insulin resistance and miR-140-5p may be served as a therapeutic target of metabolic diseases.

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“…The luciferase activity was measured after 48 h transfection by using the Dual-Luciferase Reporter Assay (Promega, Shanghai, China). 30 , 31…”

Section: Methodsmentioning

confidence: 99%

“…The luciferase activity was measured after 48 h transfection by using the Dual-Luciferase Reporter Assay (Promega, Shanghai, China). 30,31 Statistical Analysis SPSS 18.0 software was used for statistical analysis. All experiments were repeated three times and the data were presented as the mean ± standard deviation (SD).…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells

Yan

Wang

et al. 2021

DMSO

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“…The overexpression of HOPX , upregulation of p21, and downregulation of cyclin D1 and CDK4 regulate the progress of migration and invasion of MDA-MB-468 cells to modulate tumor growth of the breast [ 50 ]. Colorectal cancer (CRC) is an example where the expression of SPRR3 promotes the binding between PCAT18 and miR-759 and therefore restores a portion of the proliferation and invasion capabilities of CRC cells [ 51 ]. The combination of GO analysis and the literature review directly displays the connection between the proposed biomarker module and diverse cancers.…”

Section: Resultsmentioning

confidence: 99%

FRL: An Integrative Feature Selection Algorithm Based on the Fisher Score, Recursive Feature Elimination, and Logistic Regression to Identify Potential Genomic Biomarkers

Luo

Zhang

et al. 2021

BioMed Research International

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Accurate screening on cancer biomarkers contributes to health assessment, drug screening, and targeted therapy for precision medicine. The rapid development of high-throughput sequencing technology has identified abundant genomic biomarkers, but most of them are limited to single-cancer analysis. Based on the combination of Fisher score, Recursive feature elimination, and Logistic regression (FRL), this paper proposes an integrative feature selection algorithm named FRL to explore potential cancer genomic biomarkers on cancer subsets. Fisher score is initially used to calculate the weights of genes to rapidly reduce the dimension. Recursive feature elimination and Logistic regression are then jointly employed to extract the optimal subset. Compared to the current differential expression analysis tool GEO2R based on the Limma algorithm, FRL has greater classification precision than Limma. Compared with five traditional feature selection algorithms, FRL exhibits excellent performance on accuracy (ACC) and F1-score and greatly improves computational efficiency. On high-noise datasets such as esophageal cancer, the ACC of FRL is 30% superior to the average ACC achieved with other traditional algorithms. As biomarkers found in multiple studies are more reliable and reproducible, and reveal stronger association on potential clinical value than single analysis, through literature review and spatial analyses of gene functional enrichment and functional pathways, we conduct cluster analysis on 10 diverse cancers with high mortality and form a potential biomarker module comprising 19 genes. All genes in this module can serve as potential biomarkers to provide more information on the overall oncogenesis mechanism for the detection of diverse early cancers and assist in targeted anticancer therapies for further developments in precision medicine.

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“…Furthermore, PCAT18 promoted colorectal cancer cell proliferation, migration and invasion through binding miR-759 to promote the expression of SPRR. 13 The biological roles and mechanism of PCAT18 in human cancers are largely unknown. The current study aimed to investigate the exact roles and potential mechanism of PCAT18 in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“… 11 , 12 Nevertheless, Yang et al reported the oncogenic role of PCAT18 in colorectal cancer. 13 Obviously, the biological effects and underlying mechanism of PCAT18 in the development of main human cancers, including NSCLC, remain elusive.…”

Section: Introductionmentioning

confidence: 99%

LncRNA PCAT18 Promotes Non-Small Cell Lung Cancer Progression by Sponging miR-4319

Wang²,

Zhou

et al. 2021

CMAR

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Introduction NSCLC (non-small cell lung cancer), the most common type of human cancer, is a main cause of cancer-associated mortality. Accumulating evidence has confirmed that long non-coding RNAs serve crucial roles in NSCLC development. Methods The PCAT18 expression in NSCLC tissues and cell lines were evaluated by reverse transcription-quantitative PCR. Cell Counting Kit-8 assays, colony formation study, wound healing assays and transwell invasion assays, and tumor xenograft experiments were performed to investigate the biological functions of PCAT18 in NSCLC. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays were further used to explore the association between PCAT18 and miR-4319. Results PCAT18 expression was up-regulated in NSCLC tissues and cell lines. Furthermore, PCAT18 silencing inhibited NSCLC cell proliferation, migration and invasion, while co-transfection with a miR-4319 inhibitor reversed these biological effects, and miR-4319 inhibited NSCLC growth in vivo. Additionally, PCAT18 silencing promoted NSCLC cell apoptosis and induced G1 stage arrest. Moreover, luciferase reporter assays illustrated that PCAT18 regulated miR-4319 directly, and a RIP assay and RNA pull-down analysis further demonstrated that miR-4319 inhibited PCAT18 in a RNA-induced silencing complex-dependent manner. Finally, PCAT18 silencing impaired the growth of NSCLC in vivo. Conclusion In conclusion, these findings demonstrated that PCAT18 promoted NSCLC development by sponging miR-4319. PCAT18 may serve as a crucial biomarker for the diagnosis and targeted therapy of NSCLC.

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<p>Long Noncoding RNA PCAT18 Upregulates SPRR3 to Promote Colorectal Cancer Progression by Binding to miR-759</p>

Cited by 10 publications

References 25 publications

miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells

miR-140-5p Aggravates Insulin Resistance via Directly Targeting GYS1 and PPP1CC in Insulin-Resistant HepG2 Cells

FRL: An Integrative Feature Selection Algorithm Based on the Fisher Score, Recursive Feature Elimination, and Logistic Regression to Identify Potential Genomic Biomarkers

LncRNA PCAT18 Promotes Non-Small Cell Lung Cancer Progression by Sponging miR-4319

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