Circular RNA 0006349 Augments Glycolysis and Malignance of Non-small Cell Lung Cancer Cells Through the microRNA-98/MKP1 Axis

Background: The involvement of dysregulated circular RNAs (circRNAs) in human diseases has been increasingly recognized. In this study, we focused on the function of a newly screened circRNA, circ_0006349, in the progression of non-small-cell lung cancer (NSCLC) and the molecules of action.Methods: The NSCLC circRNA dataset GSE101684, microRNA (miRNA) dataset GSE29250, and mRNA dataset GSE51852 obtained from the GEO database were used to identify the differentially expressed genes in NSCLC samples. Tumor and normal tissues were collected from 59 patients with NSCLC. The expression of circ_0006349, miR-98, and MAP kinase phosphatase 1 (MKP1) in collected tissue samples and in acquired cells was determined. The binding relationships between miR-98 and circ_0006349/MKP1 were predicted and validated. Altered expression of circ_0006349, miR-98, and MKP1 was introduced in NSCLC cells to examine their roles in cell growth, apoptosis, and glycolysis.Results: Circ_0006349 and MKP1 were upregulated, and miR-98 was poorly expressed in the collected tumor tissues and the acquired NSCLC cell lines. Circ_0006349 was identified as a sponge for miR-98 to elevate MKP1 expression. Silencing of circ_0006349 suppressed proliferation and increased apoptosis of Calu-3 and H1299 cells, and it reduced glycolysis, glucose uptake, and the production of lactate in cells. Upon circ_0006349 knockdown, further downregulation of miR-98 or upregulation of MKP1 restored the malignant behaviors of cells.Conclusion: This research demonstrated that circ_0006349 derepressed MKP1 expression by absorbing miR-98, which augmented the proliferation and glycolysis of NSCLC cells and promoted cancer development.

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RNA-Seq profiling of circular RNAs in human small cell lung cancer

Epigenomics ◽

10.2217/epi-2019-0382 ◽

2020 ◽

Vol 12 (8) ◽

pp. 685-700 ◽

Cited By ~ 2

Author(s):

Chenxi Zhang ◽

Bin Zhang ◽

Baiyin Yuan ◽

Caiping Chen ◽

Ying Zhou ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Circular Rna ◽

Small Cell ◽

Circular Rnas ◽

Rna Seq ◽

Small Cell Lung ◽

Real Time Quantitative Pcr ◽

Generation Sequencing

Aim: We aimed to explore the circular RNA (circRNA) profile of small-cell lung cancer (SCLC). Materials & methods: Total RNA was extracted from six paired SCLC tumors and adjacent noncancerous tissues. Next-generation sequencing was performed to identify the circRNA expression profile of SCLC. Results: We found that five circRNAs were significantly upregulated and 30 circRNAs were significantly downregulated in the SCLC tissues. We confirmed the five upregulated and four randomly selected downregulated circRNAs using real-time quantitative PCR. Notably, circ-STXBP5L was selectively upregulated in SCLC samples, but undetectable in the normal control tissues. Bioinformatics analysis demonstrated that circ-STXBP5L may participate in SCLC carcinogenesis by regulating numerous cancer-related pathways. Conclusion: This study may provide new insights into the early diagnosis and development of targeted therapies for SCLC.

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A Novel Circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 Pathway Regulates Cisplatin-Resistance in Non-Small Cell Lung Cancer (NSCLC)

10.21203/rs.3.rs-50135/v1 ◽

2020 ◽

Author(s):

Xiang Zhu ◽

Jing Han ◽

Huiyin Lan ◽

Qingren Lin ◽

Yuezhen Wang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cisplatin Resistance ◽

Circular Rna ◽

Small Cell ◽

Circular Rnas ◽

Small Cell Lung

Abstract Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggested that targeting circular RNAs (circRNAs) became an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Based on this, this study identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade contributed to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, the parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin stimulation to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells, instead of CS-NSCLC cells. Further experiments validated that hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells. Interestingly, the gain- and loss-function experiments validated that knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating miR-377-3p/GOT1 axis. Furthermore, the xenograft tumor-bearing mice models were established by using the CR-NSCLC cells, and we proved that silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. In general, analysis of data suggested that targeting hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel agents to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

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Comprehensive Assessment of Serum hsa_circ_0070354 as a Novel Diagnostic and Predictive Biomarker in Non-small Cell Lung Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.796776 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yuejiao Huang ◽

Shiyi Qin ◽

Xinliang Gu ◽

Ming Zheng ◽

Qi Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Tumor Markers ◽

Cell Lung Cancer ◽

Circular Rna ◽

Small Cell ◽

Biological Behavior ◽

Circular Rnas ◽

Small Cell Lung ◽

Significant Difference

Background: More and more studies have shown that circular RNAs (circRNAs) play an essential role in the occurrence and development of tumors. Hence, they can be used as biomarkers to assist in diagnosing tumors. This study focuses on exploring the role of circular RNA (hsa_circ_0070354) in the diagnosis and prognosis of non-small cell lung cancer (NSCLC).Materials and Methods: First of all, high-throughput sequencing was used to find the difference in the expression of circular RNA between NSCLC and adjacent tissues. The circRNAs with higher differences in expression were selected to verify their expressions in tissues, cells, and serum using qRT-PCR. Secondly, the hsa_circ_0070354 with a significant difference was chosen as the research goal, and the molecular properties were verified by agarose gel electrophoresis and Sanger sequencing, etc. Then, actinomycin D and repeated freeze-thaw were used to explore the stability and repeatability of hsa_circ_0070354. Finally, the expression of hsa_circ_0070354 in serum of 133 patients with NSCLC and 97 normal donors was detected, and its sensitivity, specificity, and prognosis as tumor markers were statistically analyzed.Results: Hsa_circ_0070354 was highly expressed in tissues, cells, and serum of NSCLC, and it has the characteristics of sensitivity, stability, and repeatability. The ROC curve indicates that hsa_circ_0070354 is superior to conventional tumor markers in detecting NSCLC, and the combined diagnosis is of more significance in the diagnosis. The high expression of hsa_circ_0070354 is closely related to the late-stage, poor differentiation of the tumor and the short survival time of the patients, which is an independent indicator of poor prognosis.Conclusion: Hsa_circ_0070354 is not only a novel sensitive index for the diagnosis of NSCLC but also a crucial marker for bad biological behavior.

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Circular RNA SMARCA5 suppressed non-small cell lung cancer progression by regulating miR-670-5p/RBM24 axis

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa099 ◽

2020 ◽

Vol 52 (10) ◽

pp. 1071-1080

Author(s):

Danjie Zhang ◽

Yuefeng Ma ◽

Zhenchuan Ma ◽

Shiyuan Liu ◽

Liangzhang Sun ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Progression ◽

Cell Lung Cancer ◽

Rna Binding ◽

Circular Rna ◽

Small Cell ◽

Luciferase Reporter ◽

Circular Rnas ◽

Small Cell Lung

Abstract Circular RNAs (circRNAs) have good stability and long half-life in blood and other body fluid, and possess regulatory effects on various biological processes as miRNA/RNA-binding protein sponges, or by competing endogenous RNA, indicating their great potential as biomarkers or targets of cancer therapy. In this study, we mainly explored the role and mechanism of circular RNA SMARCA5 (circsSMARCA5) in non-small cell lung cancer (NSCLC). Quantitative RT-PCR was applied to measure the expression levels of genes, and then, the relationships among circsSMARCA5, microRNA-670-5p (miR-670-5p), and RBM24 were further analyzed. Animal and cell experiments were performed to explore the functions of circsSMARCA5 in NSCLC cells. The results showed that circsSMARCA5 was expressed at low level in NSCLC tissues and cells, while miR-670-5p had high level in NSCLC tissues. Dual luciferase reporter assay verified that miR-670-5p was the target of circsSMARCA5, and RBM24 has the binding site of miR-670-5p. Further analysis showed that circsSMARCA5 could negatively regulate miR-670-5p and had positive relationship with RBM24. Moreover, circsSMARCA5 obviously inhibited tumor growth in vivo, reduced cell proliferation and increased cell apoptosis in vitro, while miR-670-5p mimic or RBM24 knockdown could reverse these effects. Thus, circsSMARCA5 may serve as an NSCLC suppressor by regulating the miR-670-5p/RBM24 axis, and it may have the potential to be a biomarker or therapeutic target for NSCLC.

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