scholarly journals Exosome-Mediated miR-7-5p Delivery Enhances the Anticancer Effect of Everolimus via Blocking MNK/eIF4E Axis in Non-Small Cell Lung Cancer

2021 ◽  
Author(s):  
Sile Liu ◽  
Weiyuan Wang ◽  
Yue Ning ◽  
Hongmei Zheng ◽  
Yuting Zhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Efficacy ◽  
Mtor Inhibitors ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

Abstract Background Everolimus is a kind of mTOR inhibitors. Activated mitogen-activated protein kinase interacting kinases/eukaryotic translation initiation factor 4E (MNK/eIF4E) axis plays a crucial role in resistance to Everolimus in non-small cell lung cancer (NSCLC). Typically, eIF4E phosphorylation increased by mTOR inhibitors was mainly mediated by MNKs. But the mechanisms are poorly understood. Recently, extensive reprogramming of miRNA profiles has also been found after long-term mTOR inhibitor exposing. Our previous studies have confirmed that tumor suppressor miR-7-5p was decreased in A549 cells after treatment with Everolimus. Exactly, MNK1 is the target of miR-7-5p. Here, we investigated the biological functions and potential molecular mechanisms of miR-7-5p in the NSCLC undergoing treatment with Everolimus. Methods miR-7-5p level and expression of main markers of MNK/eIF4E axis were evaluated by qRT-PCR, western blot, in situ hybridization, and immunohistochemistry on NSCLC cell lines and human NSCLC samples. Proliferation, migration and invasion of NSCLC cells in culture were explored by Colony formation, CCK-8, Wound healing and Transwell assays. NSCLC cell tumorigenicity was assessed by xenotransplants in nude mice. Targeted binding of miR-7-5p to MNK1 was confirmed by the Dual-luciferase reporter assay. And the isolation and identification of exosomes were investigated by Invitrogen™ Total Exosome RNA Isolation Kit, western blot, transmission electron microscopy and Zetasizer Nano ZS90 instrument. Results Everolimus targeted mTORC1 inducing NSCLC cells to secrete miR-7-5p-loaded exosomes in Rab27A and Rab27B dependent manners. Loss of intracellular miR-7-5p induced phosphorylation of MNK/eIF4E axis, but supplement of extra exosomal miR-7-5p could reverse it. Of note, both lower expression of miR-7-5p and elevated MNK1 protein were associated with poor prognosis of NSCLC. Both endogenous miR-7-5p and exo-miR-7-5p enhanced the therapeutic efficacy of Everolimus through inhibiting the proliferation, migration, and metastasis of NSCLC in vitro and vivo. Combination of miR-7-5p with Everolimus induced apoptosis to exhibit a synergistic anticancer therapeutic efficacy via dual abrogation of MNK/eIF4E and mTOR in NSCLC. Conclusion Everolimus decreases the intracellular miR-7-5p levels through release of miR-7-5p loaded exosomes from NSCLC cells in Rab27A and Rab27B dependent manners. Either endogenous miR-7-5p or exo-miR-7-5p combined with Everolimus can enhance the anticancer efficacy via targeting MNK/eIF4E axis and mTOR. Therefore, exosome-mediated miR-7-5p delivery combined with Everolimus may be considered as a promising novel combined therapeutic strategy for NSCLC.

scholarly journals Everolimus-Induced Loss of Exosomal miR-7-5p Activates MNK/eIF4E Axis in Non-Small Cell Lung Cancer

2021 ◽  
Author(s):  
Sile Liu ◽  
Weiyuan Wang ◽  
Yue Ning ◽  
Hongmei Zheng ◽  
Yuting Zhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mtor Inhibitors ◽  
Small Cell ◽  
Translation Initiation Factor ◽  
Luciferase Reporter ◽  
Small Cell Lung

Abstract Background: Everolimus is a kind of mTOR inhibitors. Activated mitogen-activated protein kinase interacting kinases/eukaryotic translation initiation factor 4E (MNK/eIF4E) axis plays a crucial role in resistance to Everolimus in non-small cell lung cancer cells (NSCLC). Typically, eIF4E phosphorylation increased by mTOR inhibitors was mainly mediated by MNKs. But the mechanisms are poorly understood. Recently, extensive reprogramming of miRNA profiles has also been found after long-term mTOR inhibitor exposing. Our previous studies have found that tumor suppressor miR-7-5p was loss in A549 cells after treatment of Everolimus. Exactly, MNK1 is the target of miR-7-5p. Here, we analyzed levels and functions of miR-7-5p in the usage of Everolimus in NSCLC.Methods: miR-7-5p level and expression of main markers of MNK/eIF4E axis was evaluated by qRT-PCR, in situ hybridization, and immunohistochemistry on human NPC samples, and by RT-PCR, western blot on NPC cell lines. Proliferation, migration and invasion of NPC cells in culture were assessed by Colony formation, CCK-8, Wound healing and Transwell assays. NPC cell tumorigenicity was assessed by xenotransplants in nude mice. Targeted binding of miR-7-5p to MNK1 was confirmed by the Dual-luciferase reporter assay. And the isolation and identification of exosomes were invested by Invitrogen™ Total Exosome RNA Isolation Kit, western blot, transmission electron microscopy and Zetasizer Nano ZS90 instrument.Results: Everolimus stimulatedtherelease of miR-7-5p loaded exosomes from NSCLC cellsinRab27A and Rab27B dependent manners, thereby reducing the intracellular tumor suppressor miR-7-5p to attenuate the inhibition of MNK1 and promote MNK-dependent eIF4E phosphorylation. Of note, both lower miR-7-5p and positive MNK1 could act as independent poor prognostic biomarkers for NSCLC. And delivery of miR-7-5p would inhibit the poor prognosis of it. Bothendogenous miR-7-5p-5p or exo-miR-7-5p collaborated with Everolimus, not only inhibited the proliferation, migration, and metastasisof NSCLC in vitro and in vivo, but also promoted the apoptosis of NSCLC viatargeting MNK/eIF4E axis.Conclusion: Everolimus-induced loss of exosomal miR-7-5p activates MNK/eIF4E axis to blunt effectiveness of itself in NSCLC. Therefore, delivery of miR-7-5p could act as a combined therapeutic strategy for mTOR-targeted cancer therapy and prognosis.

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.

scholarly journals Exosomal miR-3180-3p Inhibits Proliferation and Metastasis of Non-Small Cell Lung Cancer by Downregulating FOXP4

2020 ◽  
Author(s):  
Tengfei Chen ◽  
Yali Liu ◽  
Chang Li ◽  
Chun Xu ◽  
Cheng Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Gene Assay ◽  
Proliferation And Metastasis

Abstract Background: Non-small cell lung cancer (NSCLC) is the most malignant cancers worldwide, but the pathogenesis is not completely known. In this study, we explored the function and mechanism of exosomes transferring miR-3180-3p in NSCLC progression.Method: The expression of miR-3180-3p of NSCLC tissues and para-carcinoma tissues was from the GEO database (GEO: GSE53882). The exosomes derived from A549 cells were identified. The proliferation, migration and invasion were measured after treatment with exosomal miR-3180-3p or transfected by miR-3180-3p mimics. The relationship between miR-3180-3p and forkhead box P4 (FOXP4) was predicted by bioinformatics tool and measured dual-luciferase reporter gene assay and western blotting. At last, mouse xenograft model of NSCLC cells was established to verify the function of exosomal miR-3180-3p in vivo.Results: We found that miR-3180-3p decreased in both NSCLC cell lines and patient tissues. Overexpression of miR-3180-3p or treatment with exosomal miR-3180-3p significantly repressed the cell proliferation and metastasis in NSCLC cell lines. Subsequently, we found miR-3180-3p performed function by downregulating FOXP4 protein expression. Furthermore, the volume and weight of nude mice tumor which expressed exosomal miR-3180-3p was significantly reduced. Conclusion: Exosomal miR-3180-3p suppresses NSCLC progression by downregulating FOXP4 expression.

Silencing circPVT1 enhances radiosensitivity in non-small cell lung cancer by sponging microRNA-1208

2021 ◽  
pp. 1-17
Author(s):  
Meifang Huang ◽  
Tianqian Li ◽  
Qing Wang ◽  
Chongxin Li ◽  
Huahua Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Underlying Mechanism ◽  
Small Cell ◽  
Nsclc Cell ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Irradiation Treatment

BACKGROUND: Radiotherapy is one of main useful therapies in non-small cell lung cancer (NSCLC). Nevertheless, the underlying mechanism between NSCLC cell radiosensitivity and effective treatment remains unclear. OBJECTIVE: The aim is to explore the relationship between circular (circ) RNA and NSCLC cell radiosensitivity. METHODS: CircRNA plasmacytoma variant translocation 1 (PVT1) and microRNA (miR)-1208 expression in NSCLC cells were assessed using quantitative reverse transcriptase PCR (qRT-PCR). NSCLC cells were transfected with si-PVT1 or miR-1208 inhibitor and then exposed to irradiation. Cellular biology behaviors were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), colony formation, invasion and western blot. Additionally, binding between circPVT1 and miR-1208 was testified by dual-luciferase reporter and RIP assay. RESULTS: CircPVT1 was upregulated in NSCLC cells after irradiation treatment. Silencing circPVT1 induced inhibition of NSCLC cell growth and invasion, accompanied by cell apoptosis and γ-H2AX expression. Moreover, NSCLC cell proliferation and invasion was further inhibited by irradiation treatment in circPVT1-silenced cells, indicating a strong radiosensitivity of NSCLC cells. CircPVT1 functions as a competing endogenous RNA towards miR-1208. Silencing miR-1208 reversed NSCLC cell sensitivity response to irradiation and activated PI3K/AKT/mTOR pathway in circPVT1-silenced cells. CONCLUSIONS: Silencing circPVT1 enhanced radiosensitivity of NSCLC cells by sponging miR-1208.

scholarly journals Long Non-coding RNA LINC00847 Induced by E2F1 Accelerates Non-small Cell Lung Cancer Progression Through Targeting miR-147a/IFITM1 Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Huan Li ◽  
Yao-kai Chen ◽  
Qiu Wan ◽  
An-qi Shi ◽  
Min Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Well Test ◽  
Small Cell Lung

Background: Long non-coding RNAs (lncRNAs) can remarkably regulate human malignancies in terms of the development and the progression. Previously, lncRNA LINC00847 (LINC00847) has been reported to present dysregulation in several tumors. However, the expression and function of LINC00847 in non-small cell lung cancer (NSCLC) have not been investigated.Methods: RT-qPCR was performed to determine the expressions of LINC00847 in collected tissue samples and cell lines. The clinical significance of LINC00847 was statistically analyzed. CCK-8 test, cell scratch test and trans-well test were used to evaluate the proliferation, invasion and migration abilities of NSCLC cells, respectively. The xenograft tumor model was constructed to confirm the effects of LINC00847 knockdown on NSCLC in vivo. Further, luciferase reporter assays and Western blot were performed to explore molecular mechanisms underlying the functions of LINC00847.Results: Increased expressions of LINC00847 were observed in NSCLC samples as well as cell lines. Additionally, E2F1 could be capable of directly binding to the LINC00847 promoter region, followed by promoting its expression. Clinically, LINC00847 high-expression could lead to poor prognosis of NSCLC patients. Functionally, LINC00847 knockdown noticeably repressed NSCLC cell growth and metastasis. Mechanically, miR-147a/IFITM1 axis was a downstream target of LINC00847, and silencing of miR-147a could rescue the anti-cancer effects of LINC00847 knockdown on NSCLC cell behaviors.Conclusion: Overall, up regulation of LINC00847 induced by E2F1 promoted the progression of NSCLC by modulating miR-147a/IFITM1 axis, representing a novel regulatory mechanism for NSCLC progression.

scholarly journals miR-202 Enhances the Anti-Tumor Effect of Cisplatin on Non-Small Cell Lung Cancer by Targeting the Ras/MAPK Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2160-2171 ◽  
Author(s):  
Wei Sun ◽  
Wei Ping ◽  
Yitao Tian ◽  
Wenbin Zou ◽  
Jiawei Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mapk Pathway ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Kras Gene

Background/Aims: KRas is usually mutated in non-small cell lung cancer (NSCLC). The mutated KRas gene is a negative prognostic indicator that promotes tumor proliferation, metastasis, and drug resistance in NSCLC, and thus has become a target for cancer therapy. This study is focused on the effects of the microRNA (miR)-202/KRas axis in regulating chemosensitivity in NSCLC. Methods: Quantitative reverse transcriptase real-time PCR analysis was performed to examine the expression of miR-202. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays were performed to evaluate the sensitivity of cisplatin against NSCLC cells. The miR-202/KRas axis was confirmed by western blot and luciferase reporter assays. Cell apoptosis was measured by flow cytometry. KRas expression, MEK1/2 and ERK1/2 phosphorylation, and activation of caspase-9 and caspase-3 were detected by western blot. Results: A significant decrease in miR-202 expression was observed in NSCLC cells both in vivo and in vitro. In addition, miR-202 expression was associated with drug resistance. Recovery of miR-202 expression levels was found to increase the sensitivity of both NCI-H441 and A549 NSCLC cells to cisplatin treatment. Mechanically, as the Ras/mitogen-activated protein kinase (MAPK) pathway was aberrantly activated in NCI-H441 and A549 NSCLC cells, the overexpression of miR-202 was found to inhibit the Ras/MAPK pathway by targeting the KRas gene. As a result, increased miR-202 expression expanded apoptosis signaling induced by cisplatin in NSCLC cells. Conclusion: The miR-202/KRas axis controlled the chemosensitivity of NSCLC by mediating the Ras/MAPK pathway. Thus, the combination of platinum-based drugs with miR-202 may represent a novel strategy to enhance the anti-tumor effect against NSCLC.

scholarly journals MicroRNA-103a Curtails the Stemness of Non-Small Cell Lung Cancer Cells by Binding OTUB1 via the Hippo Signaling Pathway

2020 ◽  
Vol 19 ◽  
pp. 153303382097164
Author(s):  
Zhenzhen Hu ◽  
Dan Xiao ◽  
Tingting Qiu ◽  
Jun Li ◽  
Zhentian Liu
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Hippo Signaling ◽  
Small Cell Lung ◽  
Luciferase Reporter Gene

Objective: Although microRNA-103a (miR-103a) dysfunction has been implicated in various cancers, its relevance to non-small cell lung cancer (NSCLC) has not been clarified. This study was conducted to examine the molecular mechanism underlying the regulatory role of miR-103a in NSCLC. Methods: Kaplan–Meier analysis was carried out to assess the relationship between overall survival of NSCLC patients and miR-103a expression. Reverse-transcription quantitative polymerase chain reaction and western blot analyses were applied to evaluate the expression of relevant genes in tissues and cells. Sphere formation, MTS, flow cytometry, and Transwell assays were performed to characterize stemness. Dual luciferase reporter gene assays were used to clarify the binding relationship between miR-103a and ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1). Finally, western blot analysis was used to assess the involvement of the Hippo pathway in NSCLC. Results: In NSCLC tissues and cells, miR-103a was expressed at low levels, whereas OTUB1 was expressed at high levels. Higher miR-103 expression levels were associated with a better prognosis for patients with NSCLC. When miR-103a was overexpressed, cell viability and stemness decreased, whereas apoptosis and cell cycle arrest were facilitated. The expression of phosphorylated YAP also decreased significantly. Opposite trends were observed after miR-103a silencing. OTUB1 expression and YAP phosphorylation decreased in the presence of miR-103a, and OTUB1 overexpression blocked the inhibitory effects of miR-103a on NSCLC cells. Conclusion: The miR-103a/OTUB1/Hippo axis may play a role in modulating the malignant behavior and stemness of cancer stem cells and thus could be a potential therapeutic target for the management of NSCLC.

scholarly journals The MicroRNA-130a-5p/RUNX2/STK32A Network Modulates Tumor Invasive and Metastatic Potential in Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Fang Ma ◽  
Yangchun Xie ◽  
Yiyu Lei ◽  
Zengshuyu Kuang ◽  
Xianling Liu
Keyword(s):  
Lung Cancer ◽  
Transcription Factor ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Small Cell Lung

Abstract Background Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells as along with metastasis in vivo, and to explore the underlying mechanism.Methods RT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-3p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays.Results miR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interacted with STK32A to promote its expression. Following the validation of the tumor-supporting role of STK32A in NSCLC cells, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo.Conclusions miR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A axis, offering possible targets for the treatment for NSCLC.

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.

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

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