The long noncoding RNA LINC01140/miR-140-5p/FGF9 axis modulates bladder cancer cell aggressiveness and macrophage M2 polarization

Wu, Shuiqing; Xu, Ran; Zhu, Xuan; He, Haiqing; Zhang, Jinhua; Qi, Zhang; Wang, Yinhuai; Zhao, Xiaokun

doi:10.18632/aging.202147

Cited by 33 publications

(26 citation statements)

References 59 publications

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“…ADAMTS9-AS2 regulates the proliferation, migration and apoptosis of BC cells by targeting miR-182-5p ( Guo et al, 2021 ). The LINC01140/miR-140-5p/FGF9 axis regulates the invasiveness of BC cells and the M2 polarization of macrophages ( Wu et al, 2020 ). LncRNA PVT1 accelerates the malignant phenotype of BC cells by regulating the miR-194-5p/BCLAF1 axis as a competing endogenous RNA ( Chen et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

Chen

Nie

et al. 2021

Front. Cell Dev. Biol.

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Background: Ferroptosis is closely related to the occurrence and development of cancer. An increasing number of studies have induced ferroptosis as a treatment strategy for cancer. However, the predictive value of ferroptosis-related lncRNAs in bladder cancer (BC) still need to be further elucidated. The purpose of this study was to construct a predictive signature based on ferroptosis-related long noncoding RNAs (lncRNAs) to predict the prognosis of BC patients.Methods: We downloaded RNA-seq data and the corresponding clinical and prognostic data from The Cancer Genome Atlas (TCGA) database and performed univariate and multivariate Cox regression analyses to obtain ferroptosis-related lncRNAs to construct a predictive signature. The Kaplan-Meier method was used to analyze the overall survival (OS) rate of the high-risk and low-risk groups. Gene set enrichment analysis (GSEA) was performed to explore the functional differences between the high- and low-risk groups. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the predictive signature and immune status. Finally, the correlation between the predictive signature and the treatment response of BC patients was analyzed.Results: We constructed a signature composed of nine ferroptosis-related lncRNAs (AL031775.1, AL162586.1, AC034236.2, LINC01004, OCIAD1-AS1, AL136084.3, AP003352.1, Z84484.1, AC022150.2). Compared with the low-risk group, the high-risk group had a worse prognosis. The ferroptosis-related lncRNA signature could independently predict the prognosis of patients with BC. Compared with clinicopathological variables, the ferroptosis-related lncRNA signature has a higher diagnostic efficiency, and the area under the receiver operating characteristic curve was 0.707. When patients were stratified according to different clinicopathological variables, the OS of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the high-risk group. ssGSEA showed that the predictive signature was significantly related to the immune status of BC patients. High-risk patients were more sensitive to anti-PD-1/L1 immunotherapy and the conventional chemotherapy drugs sunitinib, paclitaxel, cisplatin, and docetaxel.Conclusion: The predictive signature can independently predict the prognosis of BC patients, provides a basis for the mechanism of ferroptosis-related lncRNAs in BC and provides clinical treatment guidance for patients with BC.

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Section: Introductionmentioning

confidence: 99%

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

Chen

Nie

et al. 2021

Front. Cell Dev. Biol.

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“… 12 However, whether miR-140-5p is associated with insulin resistance in diabetes has not been reported yet. Multiple studies have shown that miR-140-5p is identified as a tumor suppressor, including breast cancer, 13 bladder cancer, 14 non-small cell lung cancer, 15 renal cell carcinoma. 16 At present, it is generally believed that metabolic diseases and malignant tumors share a common biological mechanism, and tumor cells have enhanced the dependence on glycolytic pathway productivity, namely Warburg effect.…”

Section: Introductionmentioning

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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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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“…HCP5 promotes cell invasion and migration by sponging miR-29b-3p and regulating HMGB1 and TLR4 expression [ 122 ]. LINC01140 can regulate miR-140-5p/FGF9 axis as ceRNA to modulate the BCa phenotype, affect macrophage M2 polarization through the tumor microenvironment, and affect BCa cell aggressiveness [ 123 ]. In contrast, MAGI2-AS3 and PLAC2 are downregulated in BCa.…”

Section: Invasion Migration and Metastasismentioning

confidence: 99%

“…In addition, lower expression of 7 lncRNAs predicted shorter OS [ 24 , 26 , 57 , 126 , 150 , 152 , 186 ]. High expression of 28 lncRNAs predicted shorter OS [ 23 , 27 , 32 , 39 , 40 , 45 , 50 , 53 , 60 , 83 , 94 , 100 , 118 , 121 , 123 , 128 , 130 , 137 , 141 , 146 , 155 , 156 , 162 , 164 , 185 , 192 , 194 , 197 ].…”

Section: Lncrnas That Influence Patient Prognosismentioning

confidence: 99%

Biological functions and clinical significance of long noncoding RNAs in bladder cancer

et al. 2021

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Bladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.

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The long noncoding RNA LINC01140/miR-140-5p/FGF9 axis modulates bladder cancer cell aggressiveness and macrophage M2 polarization

Cited by 33 publications

References 59 publications

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

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

Biological functions and clinical significance of long noncoding RNAs in bladder cancer

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