Circular RNA circ<scp>CRIM</scp>1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

Wang, Lin; Liang, Yantao; Mao, Qixing; Xia, Wenjie; Chen, Bing; Shen, Huan; Xu, Lin; Jiang, Feng; Dong, Gaochao

doi:10.1111/cas.14131

Cited by 60 publications

(49 citation statements)

References 38 publications

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“…Further studies on circRNAs might provide new insights that will improve our understanding of pathological mechanisms and improve the prevention and diagnosis of related diseases. Previous studies have shown that circRNAs might be involved in the pathogenesis of lung cancer [15,16]. However, the exact roles of circRNAs in lung adenocarcinoma are far from known.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

Huang

et al. 2020

J Exp Clin Cancer Res

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Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. Methods: In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gainand loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. Results: We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain-and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Conclusions: Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

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Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

Huang

et al. 2020

J Exp Clin Cancer Res

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“…Our results suggest, for the first time, that cESRP1 may play a role in SCLC chemoresistance and serve as a valuable prognostic biomarker for patients with SCLC. LD limited-stage diseases, ED extensive-stage disease Some circRNAs have been well characterised to function as miRNA sponges in tumorigenesis [11,47,49,[65][66][67]. To better understand the potential role of cESRP1 in SCLC chemoresistance, we confirmed that cESRP1 was primarily located in the cytoplasm, which indicated that cESRP1 may function as an miRNA sponge in SCLC.…”

Section: Discussionmentioning

confidence: 52%

“…These findings suggest that miRNAs may not be degraded by cESRP1, as previously described [47]. Based on the results of previous studies [49][50][51][52], we focused on miR-93-5p, miR-182-5p, and miR-125a-5p and further investigated their roles in chemoresistance in SCLC cells. Using specific miRNA inhibitors, we successfully downregulated the expression of these three miRNAs in SCLC cells (Fig.…”

Section: Cesrp1 May Function As a Sponge Of Mir-93-5p In Sclcmentioning

confidence: 55%

Circular RNA cESRP1 sensitises small cell lung cancer cells to chemotherapy by sponging miR-93-5p to inhibit TGF-β signalling

et al. 2019

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Circular RNAs (circRNAs) are novel RNA molecules that play important roles in chemoresistance in different cancers, including breast and gastric cancers. However, whether circRNAs are involved in the response to chemotherapy in small cell lung cancer (SCLC) remains largely unknown. In this study, we observed that cESRP1 (circular RNA epithelial splicing regulatory protein-1) expression was significantly downregulated in the chemoresistant cells compared with the parental chemosensitive cells. cESRP1 enhanced drug sensitivity by repressing miR-93-5p in SCLC. Cytoplasmic cESRP1 could directly bind to miR-93-5p and inhibit the posttranscriptional repression mediated by miR-93-5p, thereby upregulating the expression of the miR-93-5p downstream targets Smad7/p21(CDKN1A) and forming a negative feedback loop to regulate transforming growth factor-β (TGF-β) mediated epithelial-mesenchymal transition. Furthermore, cESRP1 overexpression and TGF-β pathway inhibition both altered tumour responsiveness to chemotherapy in an acquired chemoresistant patient-derived xenograft model. Importantly, cESRP1 expression was downregulated in SCLC patient tissues and was associated with survival. Our findings reveal, for the first time, that cESRP1 plays crucial a role in SCLC chemosensitivity by sponging miR-93-5p to inhibit the TGF-β pathway, suggesting that cESRP1 may serve as a valuable prognostic biomarker and a potential therapeutic target in SCLC patients.

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“…Lung adenocarcinoma is prone to metastasis in the early stage, while brain metastasis is a common complication of lung adenocarcinoma, and its incidence increases with the prolongation of survival [21].The most common mutant gene types of lung adenocarcinoma are EGFR, KRAS, etc [22,23], which have corresponding targeted drug therapy, but are prone to drug resistance to targeted drugs. However, a large number of studies have shown that the dysregulation of circRNAs plays a crucial role in the development of LUAC; therefore, further understanding of the biological mechanism of abnormally expressed circRNAs is essential for the discovery of new, promising therapeutic targets for LUAC [24]. YU et al [25] collected 36 paired LUAC and healthy tissues and concluded that circRNA CMRA was signi cantly downregulated in cancer tissues, and circRNA cMras overexpression inhibited LUAC growth and metastasis, and its expression was negatively correlated with tumor stage.…”

Section: Discussionmentioning

confidence: 99%

Advances in Research on the circRNA-miRNA-mRNA regulatory network in lung adenocarcinoma by analysis of microarray data

Yao

Pang

et al. 2020

Preprint

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Background: The present researches indicate that circular RNAs (circRNAs) play pivotal roles in the generation and development of human cancers. However, function of circRNAs in lung adenocarcinoma is still unknown. Herein, we focused our study on the regulation mechanism of circRNAs in lung adenocarcinoma (LUAC)Methods: CircRNAs-related data can be downloaded from Gene Expression Omnibus(GEO) microarray databases. Relevant expression data of miRNAs and mRNAs were obtained from The Cancer Genome Atlas (TCGA) databases. The differentially expressed circRNAs (DEcircRNAs) were obtained by the robust rank aggregation method, and constructed a ceRNA network with circRNA-miRNA pairs and miRNA-mRNA pairs. The function and pathway enrichment of different genes were analyzed, and the protein-protein interaction (PPI) was predicted by String software, and the subnetwork management module was constructed by MCODE plugin. The differentially expressed mRNAs (DEmRNAs) were used to establish survival analysis by R software.Results: A total of 19 up-regulated circRNAs, 45 down-regulated circRNAs, 98 up-regulated miRNAs, 18 down-regulated miRNAs, 2002 up-regulated mRNAs, and 553 down-regulated mRNAs were obtained in lung adenocarcinoma. The circRNA-miRNA-mRNA network was constructed by six circRNAs (hsa_circ_0003528, hsa_circ_0004315, hsa_circ_0005699, hsa_circ_0002588, hsa_circ_0005777, hsa_circ_0027033), 19 miRNAs and 33 mRNAs. GO and KEGG pathway analysis indicated that DEmRNAs might be related to the progression of LUAC. The PPI network was constructed and four hub genes (CEP55, CHEK1, CDC25A, KIF23) were obtained from the network, and four hub genes were found to be associated with the same miRNA and circRNA, including hsa_circ_0004315/hsa-miR-195/CEP55, CHEK1, CDC25A, KIF23. Three hub genes (CEP55, CHEK1, KIF23) were significantly associated with LUAC survival and prognosis, and the overall survival rate of lung adenocarcinoma was decreased in high-expression genes compared with low-expression genes.Conclusion: Our finding indicated that circRNA-miRNA- mRNA axis paly key role in the pathogenesis of lung adenocarcinoma, and some circRNAs could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients.

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Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)‐182/miR‐93‐leukemia inhibitory factor receptor pathway

Cited by 60 publications

References 38 publications

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

Circular RNA cESRP1 sensitises small cell lung cancer cells to chemotherapy by sponging miR-93-5p to inhibit TGF-β signalling

Advances in Research on the circRNA-miRNA-mRNA regulatory network in lung adenocarcinoma by analysis of microarray data

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