scholarly journals Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer

2018 ◽  
Vol 51 (5) ◽  
pp. 2324-2340 ◽  
Author(s):  
Xiuyuan Li ◽  
Zenglei Zhang ◽  
Hua Jiang ◽  
Qiang Li ◽  
Ruliang Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Promoter Region ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Background/Aims: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. Methods: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines. Fluorescence in situ hybridization analysis (FISH) assay was used for the identification of sublocation of circPVT1 in NSCLC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to verify the binding of c-Fos at circPVT1 promoter region, and the direct interaction between circPVT1 and miR-125b. Gain- or loss-function assays were performed to evaluate the effects of circPVT1 on cell proliferation and invasion. Western blot and immunohistochemistry assays were performed to detect the protein levels involved in E2F2 pathway. Results: We found that circPVT1 was upregulated in NSCLC specimens and cells. The transcription factor c-Fos binded to the promoter region of circPVT1, resulting in the overexpression of circPVT1 in NSCLC. Knockdown of circPVT1 suppressed NSCLC cell proliferation, migration and invasion, and increased apoptosis. In addition, circPVT1 mediated NSCLC progression via the regulation of E2F2 signaling pathway. More importantly, circPVT1 was predominantly abundant in the cytoplasm of NSCLC cells, and circPVT1 could serve as a competing endogenous RNA to regulate E2F2 expression and tumorigenesis in a miR-125b-dependent manner, which is further verified by using an in vivo xenograft model. Conclusion: circPVT1 promotes NSCLC cell growth and invasion, and may serve as a promising therapeutic target for NSCLC patients. Therefore, silence of circPVT1 could be a future direction to develop a novel treatment strategy.

scholarly journals MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1

2019 ◽  
Vol 27 (8) ◽  
pp. 879-887 ◽  
Author(s):  
Wei Wu ◽  
Linyan He ◽  
Yan Huang ◽  
Likun Hou ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Kinase Signaling ◽  
Small Cell Lung ◽  
Proliferation And Invasion

An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues. miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510 suppressed NSCLC cell proliferation and invasion in vitro. We identified SRC kinase signaling inhibitor 1 (SRCIN1) as a direct target gene of miR-510 in NSCLC. Expression of SRCIN1 was downregulated in lung cancer cells and negatively correlated with miR-510 expression in tumor tissues. Downregulation of SRCIN1, leading to inhibition of miR-510 expression, reversed cell proliferation and invasion in NSCLC cells. These results showed that miR-510 acted as an oncogenic miRNA in NSCLC, partly by targeting SRCIN1, suggesting that miR-510 can be a potential approach for the treatment of patients with malignant lung cancer.

Circular RNA hsa_circ_0102231 sponges miR-145 to promote non-small cell lung cancer cell proliferation by up-regulating the expression of RBBP4

2020 ◽  
Author(s):  
Xueru Cao ◽  
Fengzhen Li ◽  
Jianping Shao ◽  
Jianmei Lv ◽  
Ailan Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Promoter Activity ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Assay ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Abstract Circular RNAs (circRNAs) are important regulators in various cancers. Previous studies have found that hsa_circ_0102231 is an oncogene in lung adenocarcinoma. Here we investigated its mechanism in the development of non-small cell lung cancer (NSCLC). We detected the levels of hsa_circ_0102231 in five NSCLC cell lines and one normal bronchial epithelium cell line. The interaction between hsa_circ_0102231 and miR-145 was predicted and confirmed by pull-down and luciferase assays. The nuclear mass separation assay and fluorescence in-situ hybridization were used to detect the distribution of hsa_circ_0102231. CCK-8 and Transwell assays were used to assess the cell proliferative and invasive ability. Western blot and RT-qPCR, respectively, detected the protein and mRNA levels of RBBP4. The RBBP4 promoter activity was detected with luciferase assay. We found that hsa_circ_0102231 level was higher in NSCLC cells. hsa_circ_0102231 is mainly localized to the cytoplasm. hsa_circ_0102231 promotes NSCLC cell proliferation and invasion by sponge for miR-145. miR-145 significantly decreases the RBBP4 promoter activity, and its mRNA and protein levels. RBBP4 is an oncogene to promotes proliferation and invasion ability. Our findings suggest that hsa_circ_0102231 promotes proliferation and invasion by mediating the miR-145/RBBP4 axis in NSCLC, indicating that it might be a potential target for NSCLC treatment.

scholarly journals The Long Non-Coding RNA XIST Controls Non-Small Cell Lung Cancer Proliferation and Invasion by Modulating miR-186-5p

2017 ◽  
Vol 41 (6) ◽  
pp. 2221-2229 ◽  
Author(s):  
Haoyou Wang ◽  
Qiming Shen ◽  
Xin Zhang ◽  
Chunlu Yang ◽  
Su Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Background/Aims: Long non-coding RNAs (lncRNAs) are key players in the development and progression of human cancers. The lncRNA XIST (X-inactive specific transcript) has been shown to be upregulated in human non-small cell lung cancer (NSCLC); however, its role and molecular mechanisms in NSCLC cell progression remain unclear. Methods: qRT-PCR was conducted to assess the expression of XIST and miR-186. Cell proliferation was detected using MTT assay. Cell invasion and migration were evaluated using transwell assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Luciferase reporter assay was used to identify the direct regulation of XIST and miR-186. A RNA immunoprecipitation was used to analyze whether XIST was associated with the RNA-induced silencing complex (RISC). Results: We confirmed that XIST was upregulated in NSCLC cell lines and tissues. Functionally, XIST knockdown inhibited cancer cell proliferation and invasion, and induced apoptosis in vitro, and suppressed subcutaneous tumor growth in vivo. Mechanistic investigations revealed a reciprocal repressive interaction between XIST and miR-186-5p. Furthermore, we showed that miR-186-5p has a binding site for XIST. Our data also indicated that XIST and miR-186-5p are likely in the same RNA induced silencing complex. Conclusion: Together, our data revealed that XIST knockdown confers suppressive function in NSCLC and XIST may be a novel therapeutic marker in this disease.

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

scholarly journals Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Yunpeng Liu ◽  
Xingyu Lin ◽  
Shiyao Zhou ◽  
Peng Zhang ◽  
Guoguang Shao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: The HOXA cluster antisense RNA 2 (HOXA-AS2) has recently been discovered to be involved in carcinogenesis in multiple cancers. However, the role and underlying mechanism of HOXA-AS2 in non-small cell lung cancer (NSCLC) yet need to be unraveled. Methods: HOXA-AS2 expression in NSCLC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). Furthermore, the effects of HOXA-AS2 on NSCLC cell proliferation, apoptosis, migration, and invasion were assessed by MTS, flow cytometry, wound healing and transwell invasion assays, respectively. Starbase2.0 predicted and luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the association of HOXA-AS2 and miR-520a-3p in NSCLC cells. Results: Our results revealed that HOXA-AS2 in NSCLC tissues were up-regulated and cell lines, and were associated with poor prognosis and overall survival. Further functional assays demonstrated that HOXA-AS2 knockdown significantly inhibited NSCLC cell proliferation, induced cell apoptosis and suppressed migration and invasion. Starbase2.0 predicted that HOXA-AS2 sponge miR-520a-3p at 3′-UTR, which was confirmed using luciferase reporter and RIP assays. miR-520a-3p expression was inversely correlated with HOXA-AS2 expression in NSCLC tissues. In addition, miR-520a-3p inhibitor attenuated the inhibitory effect of HOXD-AS2-depletion on cell proliferation, migration and invasion of NSCLC cells. Moreover, HOXA-AS2 could regulate HOXD8 and MAP3K2 expression, two known targets of miR-520a-3p in NSCLC. Conclusion: These findings implied that HOXA-AS2 promoted NSCLC progression by regulating miR-520a-3p, suggesting that HOXA-AS2 could serve as a therapeutic target for NSCLC.

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