The functional roles of the circRNA/Wnt axis in cancer

Xue, Chen; Li, Ganglei; Zheng, Qiuxian; Gu, Xinyu; Bao, Zhengyi; Lü, Juan; Li, Lanjuan

doi:10.1186/s12943-022-01582-0

Cited by 69 publications

(48 citation statements)

References 321 publications

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“…Circular RNA (circRNA), an endogenous noncoding RNA with a covalently closed-loop structure but without a 5′ cap and 3′ polyadenylate tail, is resistant to exonucleases [ 7 ]. A large number of previous studies have confirmed the presence of circRNAs in a variety of diseases and cancers [ 8 ]. Some reports revealed the involvement and different roles of many circRNAs in the development of LUAD.…”

Section: Introductionmentioning

confidence: 99%

Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis

et al. 2022

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Objective. To clarify the potential function and molecular mechanism of calycosin in lung adenocarcinoma (LUAD) cells. Methods. LUAD cells (A549 and H1299) were treated with calycosin at different concentrations (25 nM, 50 nM, and 100 nM) for 24 h. The colony formation, invasion, and migration of the cells were assessed by colony formation, transwell, and scratch assays, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the mRNA expression level of circ_0001946, miR-21, glycerol-3-phosphate dehydrogenase 1 like (GPD1L), and hypoxia-inducible factor-1α (HIF-1α) in clinical tissue samples and LUAD cells. RNA pull-down assay and dual-luciferase reporter assay were performed to verify the relationship among circ_0001946, miR-21, GPD1L, and HIF-1α. Western blot was performed to detect the protein expression of epithelial-mesenchymal transition (EMT) process-related genes (E-cadherin, N-cadherin, and snail) and GPD1L as well as HIF-1α. Results. Calycosin inhibited colony formation, invasion, migration, and EMT progression in A549 and H1299 cells. Besides, calycosin was able to regulate the expression of circ_0001946, miR-21, GPD1L, and HIF-1α in LUAD cells. According to the findings of QRT-PCR, the expression level of circ_0001946 and GPD1L in LUAD tissues was significantly lower than that in adjacent noncancerous normal tissues, and the expression of miR-21 and HIF-1α was also significantly increased in clinical tissue samples. In addition, there was a targeted regulatory relationship among the above four expressions. Knockdown of circ_0001946 expression in A549 cells treated with calycosin enhanced the malignant behavior of A549 cells and inhibited the anticancer effect of calycosin. However, the knockdown of miR-21 promoted the anticancer effect of calycosin and inhibited the malignant behavior of A549. Conclusion. Calycosin can inhibit colony formation, invasion, migration, and EMT process of LUAD cells via regulating the circ_0001946/miR-21/GPD1L/HIF-1α signaling axis and could be a promising therapeutic drug for LUAD.

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Section: Introductionmentioning

confidence: 99%

Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis

et al. 2022

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“…In recent years, there have been a large amount of studies on circular RNAs, and now we have better understanding of the roles of circular RNAs in biogenesis and biology. However, the regulatory functions and corresponding mechanisms in many diseases, especially tumors, are still not thoroughly studied [41][42][43][44][45][46]. At present, there are relatively few reports on the development, metastasis and drug resistance of circRNAs in ESCC, and the specific mechanism needs to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA hsa_circ_0003823 promotes the Tumor Progression, Metastasis and Apatinib Resistance of Esophageal Squamous Cell Carcinoma by miR-607/CRISP3 Axis

Wang¹,

Zhao²,

Sun³

et al. 2022

Int. J. Biol. Sci.

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Background: Circular RNAs (CircRNAs) have attracted a growing interest of research in cancer. The regulatory roles and mechanisms of circRNAs in progression, metastasis and drug resistance of esophageal squamous cell carcinoma (ESCC) needed to be clarified. Our previous study revealed the crucial role of Apatinib in ESCC therapy. However, the correlation between circRNAs and Apatinib resistance remained unclear. Methods: 3 pairs of tumor and paracancerous tissues of ESCC patients were used for RNA sequencing. Western blot analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, apoptosis and animal assays were conducted to confirm the roles and specific mechanisms of hsa_circ_0003823 as well as the effects of it on Apatinib sensitivity in ESCC. Results: Our results revealed that hsa_circ_0003823 was highly expressed in ESCC and associated with poor prognosis. Further results indicated that hsa_circ_0003823 promoted proliferation and metastasis ability of ESCC. In the section of mechanism experiments, hsa_circ_0003823 regulated CRISP3 by targeting microRNA-607 (miR-607) to promote progression of ESCC. Besides, we found that silencing hsa_circ_0003823 improved Apatinib sensitivity. hsa_circ_0003823 resulted in Apatinib resistance by miR-607/CRISP3 axis. Conclusions: In this study, we elucidated the function of hsa_circ_0003823 and its role in promoting tumor progression, metastasis and Apatinib resistance of ESCC through miR-607/CRISP3 axis.

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“…circRNA is a new type of noncoding RNA member composed of one or more spliced exons or introns, which has the characteristics of conservation, richness, and tissue specificity, so it may play a special molecular marker role in some diseases (such as tumors) [25]. circRNA can regulate gene expression by alternative splicing, regulating the expression of parental genes, and acting as a scaffold for protein complex assembly and RNA protein interaction and affect the occurrence and development of tumors [26,27].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of hsa_circ_0061817 Can Inhibit the Proliferation and Invasion of Lung Cancer Cells Based on Active Compounds

Zhong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. This study was aimed at investigating the expression level of hsa_circ_0061817 in lung adenocarcinoma cells and its effect on cell proliferation and invasion and the possible mechanism of hsa_circ_0061817 in lung adenocarcinoma. Methods. The overexpression plasmids of hsa_circ_0061817 (OE-hsacirc_0061817) were transfected into human lung A549 cells and mouse LLC-LUC cells, respectively. The cell viability was detected by CCK-8, and the cell proliferation was detected by cell clone formation assay and EdU assay. Transwell test was used to detect the ability of cell invasion, and apoptosis was detected by flow cytometry. WB was applied to determine the expression of apoptosis and epithelial mesenchymal transition-(EMT-) related proteins and also target proteins for observation the effect of OE-hsa_circ_0061817 on the growth of A549 cells in nude mice. Bioinformatics method was used to predict the binding microRNA (miRNA) of hsa_circ_0061817 and construct the regulatory network of competitive endogenous RNA (ceRNA) and functional analysis of miRNA target genes. Results. Compared with PLO-ciR group, the cell viability, proliferation, and invasive ability of A549 and LLC-LUC were significantly reduced in OE-hsa_circ_00061817 group, while the apoptosis increased in OE-hsa_circ_00061817 group compared to PLO-ciR group. WB results showed that the expression of caspase 3, caspase 7, caspase 9, and E-cadherin increased significantly, while the expression levels of vimentin and N-cadherin decreased severely. Most importantly, OE-hsa_circ_00061817 inhibited the growth of A549 tumor-bearing nude mice. According to TargetScan and mirBase databases, hsa_circ_0061817 may competitively bind hsa_mir-181b-3p, hsa-mir-337-3p, hsa-mir-421, and hsa-mir-548d-3p. The results of functional enrichment showed that miRNA target genes were involved in many cancer-related biological processes, including negative regulation of apoptosis, gene expression, transcriptional imbalance in cancer, transforming growth factor-β, and P53 signal pathway. Conclusions. Over expression of hsa_circ_0061817 inhibits the proliferation of lung adenocarcinoma A549 and LLC-LUC cells and may reduce the invasive ability of lung adenocarcinoma cells by weakening the process of EMT, which provides a new target for the prevention and treatment of lung adenocarcinoma.

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The functional roles of the circRNA/Wnt axis in cancer

Cited by 69 publications

References 321 publications

Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis

Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis

Circular RNA hsa_circ_0003823 promotes the Tumor Progression, Metastasis and Apatinib Resistance of Esophageal Squamous Cell Carcinoma by miR-607/CRISP3 Axis

Overexpression of hsa_circ_0061817 Can Inhibit the Proliferation and Invasion of Lung Cancer Cells Based on Active Compounds

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