scholarly journals Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Wenguang Pang ◽  
Fengliu Huang ◽  
Xin Zhang ◽  
Min Ye ◽  
Yanming Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Objective: Non-small cell lung cancer (NSCLC) continues to top the list of cancer mortalities worldwide. Early diagnosis and therapeutic interventions targeting NSCLC is becoming the world’s significant challenge. Circular RNAs (circRNAs) are emerging as a group of potential cancer biomarkers. Materials and methods: Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of circ_0072309 in NSCLC tissues and cell lines. Cell counting kit 8 (CCK-8), wound healing and Transwell assays were used to analyze cell proliferation, migration and invasion in A549 and H1299 cells. The relationship between circ_0072309 and miR-580-3 was analyzed by Luciferase reporter and RNA pull down assays. Results: We screened circ_0072309 from Gene Expression Omnibus and found that circ_0072309 was lowly expressed in NSCLC tissues and cell lines. The transfection of circ_0072309-overexpressing vector significantly suppressed the cell proliferation, migration and invasion in A549 and H1299 cells. We predicted that miR-580-3p is a target of circ_0072309 by using publicly available bioinformatic algorithms Circinteractome tool and confirmed that circ_0072309 directly bound to miR-580-3p. Furthermore, the addition of miR-580-3p mitigated the blockage of cell proliferation, migration and invasion induced by circ_0072309. Conclusions: These data showed that circ_0072309 inhibits the progression of NSCLC progression via blocking the expression of miR-580-3p. These findings revealed the anti-tumor role of circ_0072309 during the development of NSCLC and provided a novel diagnostic biomarker and potential therapy for NSCLC.

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 Long Noncoding RNA DNAH17-AS1 Promotes Tumorigenesis and Metastasis of Non-Small Cell Lung Cancer via Regulating miR-877-5p/CCNA2 Pathway

2020 ◽  
Author(s):  
Li-juan Du ◽  
Long-jun Mao ◽  
Rui-jun Jing
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: A growing number of studies have revealed that long noncoding RNAs (lncRNAs) can function as important oncogenes or tumor suppressors. This study aimed to investigate the regulatory role of lncRNA DNAH17 antisense RNA 1 (DNAH17-AS1) on non-small cell lung cancer (NSCLC) and the underlying molecular mechanisms.Methods: RT-PCR was used to examine the expression of DNAH17-AS1, miR-877-5p and CCNA2 in NSCLC specimens and cell lines. The diagnostic and prognostic values of DNAH17-AS1 expression in NSCLC patients were statistically analyzed. We also evaluated the effects of DNAH17-AS1 on the proliferation, migration, invasion and apoptosis of H1299 and 95D cells. Bioinformatic analysis and luciferase reporter assays were carried to confirm the molecular binding.Results: The expression of DNAH17-AS1 and CCNA2 mRNA was distinctly upregulated in NSCLC specimens and cell lines, while miR-877-5p expression was significantly decreased. DNAH17-AS1 could be used to distinguish NSCLC specimens from adjacent non-tumor tissues. Clinical assays revealed that high DNAH17-AS1 was associated with TNM stage, distant metastasis and shorter overall survival and disease-free survival. Functional assays indicated that knockdown of DNAH17-AS1 suppressed the proliferation, migration and invasion of H1299 and 95D cells, and promoted apoptosis. Mechanically, DNAH17-AS1 served as competing endogenous RNA (ceRNA) for miR-877-5p to positively recover CCNA2.Conclusion: We identified a novel NSCLC-related lncRNA, DNAH17-AS1 which may exert an oncogenic function via serving as a sponge for miR-877-5p to upregulate CCNA2. Our study presents novel insights into NSCLC progression and provided a prospective therapeutic target for NSCLC.

scholarly journals Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xueliang Xu ◽  
Rong Tao ◽  
Liying Sun ◽  
Xia Ji
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Colony Formation ◽  
Small Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Cyclin Dependent Kinase ◽  
Small Cell Lung

Abstract Background Circular RNAs (circRNAs) play crucial roles in the development and progression of human cancers, including non-small cell lung cancer (NSCLC). However, most of these circRNAs, such as hsa_circ_0014235, are not fully identified in functions and mechanisms. Methods The isolated exosomes from serum specimens were identified using transmission electron microscopy (TEM). The expression of hsa_circ_0014235, miR-520a-5p and cyclin-dependent kinase 4 (CDK4) was detected by real-time quantitative polymerase chain reaction (qPCR). For functional assays, cell proliferation, colony formation ability, migration, invasion, cell apoptosis and cell cycle progression were determined using cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell assay and flow cytometry assay, respectively. The expression of CDK4 and other indicated marker proteins was detected by western blot. The predicted target relationship between miR-520a-5p and hsa_circ_0014235 or cyclin-dependent kinase 4 (CDK4) was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. Results The expression of hsa_circ_0014235 was notably elevated in NSCLC serum-derived exosomes, tumor tissues and cells. NSCLC serum-derived exosomes promoted NSCLC cell resistance to cisplatin (DDP), cell proliferation, migration and invasion in vitro, as well as tumor growth and DDP resistance in vivo. Hsa_circ_0014235 overexpression enhanced DDP resistance and facilitated cell malignant behaviors. MiR-520a-5p was a target of hsa_circ_0014235, and rescue experiments showed that miR-520a-5p restoration reversed the effects of hsa_circ_0014235 overexpression. Moreover, CDK4 was a target of miR-520a-5p, and rescue experiments showed that CDK4 knockdown reversed the aggressive effects of miR-520a-5p inhibition on NSCLC progression. Conclusions Exosome-transmitted hsa_circ_0014235 promoted NSCLC malignant development by mediating the miR-520a-5p/CDK4 regulatory axis.

MicroRNA-221-3p promotes proliferation and invasion in non-small cell lung cancer via targeting Axin2 to regulate Wnt/β-catenin signaling pathway

2020 ◽  
Author(s):  
Jiangnan Zheng ◽  
Lingyun Dong ◽  
Xiaoyun Hu ◽  
Ying Xiao ◽  
Qiaozhen Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Proliferation And Invasion

Abstract ObjectiveThe mortality rate of lung cancer ranks first in malignant tumors. Among them, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer patients. In this study, we explore part of the mechanism of development and progression of NSCLC.Methods/ ResultsFirstly, there was an increase in microRNA-221-3p (miR-221-3p) expression and a decrease in Axin2 expression in NSCLC tissues using real-time reverse transcription polymerase chain reaction. Further studies showed that miR-221-3p inhibited the expression of Axin2, which negatively regulated the Wnt signaling pathway. With the method of inhibiting and overexpressing the expression of miR-221-3p and/or Axin2 respectively in NSCLC cell lines A549 and H1975, we found that inhibiting the expression of miR-221-3p leaded to a decrease in cell proliferation, migration and invasion, just like the results of overexpressing Axin2. Relatively speaking, overexpression of miR-221-3P in NSCLC cell lines showed the increase of proliferation as well as the decrease of apoptosis. Thus, we knew that miR-221-3p promoted the migration and invasion of NSCLC cells in vitro. What’s more, according to western blot and EdU assay, we demonstrated that overexpression of miR-221-3p inhibited the expression of Axin2 and subsequently activate classical Wnt/β-catenin signaling pathway. At last, a series of methods were used to identify that miR-221-3p inhibited Axin2 expression, increased cell proliferation, invasion and migration, and decreased cell apoptosis.ConclusionOur results suggest that miR-221-3p inhibits the expression of Axin2 and indirectly activates the typical Wnt/β-catenin signaling pathway, thus promoting tumor proliferation and invasion in NSCLC.

scholarly journals MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes mediated proliferation, migration and invasion of non-small cell lung cancer cells

2020 ◽  
Author(s):  
Dan Wang ◽  
Shufang Yu ◽  
Shasha Yi ◽  
Sichan Liu
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor, and its recurrence and metastasis are the main causes of death. Recently, there are evidences that tumor derived exosomes play an important role in the occurrence and development of non-small cell lung cancer.Material/Methods: First, miR-185-5p and RAB35 expression in tumor tissues, paracancerous healthy tissues, lung cancer cell lines and normal bronchial epithelial cell line were detected. Then, miR-185-5p and RAB35 were over-expressed/knocked down to study their effects on A549 cells and H2170 cells proliferation, migration and invasion . Next, bioinformatics analysis and luciferase reporter gene analysis verified the targeting relationships of miR-185-5p and RAB35 , respectively. Finally, the exosomes secreted by tumor cells with RAB35 gene downregulated or miR-185-5p overexpression were co cultured with their parent cells to verify the regulatory effect of RAB35 on the secretion and function of exosomes.Results: The miR-185-5p expression was downregulated, while RAB35 expression was prominently upregulated in NSCLC tissues and cell lines. Moreover, miR-185-5p overexpression or RAB35 downregulated suppressed cells proliferation, migration and invasion. Furthermore, we clarified that RAB35 was a direct target of miR-185-5p. Additionally, exosomes derived from tumor cells could restore cells proliferation, migration and invasion, while exosomes secreted by tumor cells with RAB35 downregulated or mR-185-5p overexpression lose the ability to restore cells proliferation, migration and invasion.Conclusions: Our findings indicate that miR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of NSCLC cells.

scholarly journals LncRNA PCGEM1 induces proliferation and migration in non-small cell lung cancer cells through modulating the miR-590-3p/SOX11 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huanshun Wen ◽  
Hongxiang Feng ◽  
Qianli Ma ◽  
Chaoyang Liang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Carcinogenic Effect

Abstract Background Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers. As reported, long non-coding RNAs (lncRNAs) induce various biological behaviors in cancers. LncRNA PCGEM1 prostate-specific transcript (PCGEM1) is reported to exert carcinogenic effect on certain cancers. Our research aimed to explore the role of PCGEM1 in NSCLC. Methods We enrolled forty NSCLC patients to explore PCGEM1 expression in clinical NSCLC tissues. Colony formation assay, CCK-8, Transwell assay were conducted to reveal cell proliferation, viability, migration and invasion. Luciferase reporter assay, RNA pull down, and RIP assay were performed to investigate the downstream axis of PCGEM1. Results PCGEM1 was significantly upregulated in NSCLC cells and tissues. Subsequently, in vitro loss-of-function experiments illustrated the carcinogenic role of PCGEM1 in NSCLC through promoting viability, proliferation, migration, and invasion. MiR-590-3p was confirmed to be a downstream gene of PCGEM1. Furthermore, SRY-box transcription factor 11 (SOX11) was verified to be a target of miR-590-3p. Additionally, rescue experiments indicated that miR-590-3p inhibitor or pcDNA3.1/SOX11 rescued the impacts of downregulated PCGEM1 on NSCLC cell proliferation, viability, migration and invasion. Conclusions LncRNA PCGEM1 aggravated proliferative and migrative abilities in NSCLC via the miR-590-3p/SOX11 axis.

scholarly journals Circ_0018534 Promotes Non-Small Cell Lung Cancer Progression by Upregulating BTBD7 via Sponging miR-153-3p

2021 ◽  
Author(s):  
Haoran Bai ◽  
Lihua Zhu ◽  
Hegen Li ◽  
Lei Zhou
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Nsclc Patient ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor in lung. In this study, we aimed to explore the role and underlying mechanism of circular RNA 0018534 (circ_0018534) in NSCLC progression.Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of circ_0018534, microRNA-153-3p (miR-153-3p) and BTB/POZ domain-containing protein 7 (BTBD7) in NSCLC tissues and cells. Protein expression was measured by western blot analysis. The morphological features of obtained NSCLC patient tissues were observed by haematoxylin and eosin staining assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, and transwell migration and invasion assays were used to examine cell viability, proliferation, apoptosis, migration and invasion, respectively. Bioinformatics analysis and dual-luciferase reporter assay were carried out to determine the interaction among circ_0018534, miR-153-3p and BTBD7. Furthermore, lentivector for short hairpin RNA against circ_0018534 (sh-circ_0018534) was used to decrease circ_0018534 expression in an animal tumor model.Results: Circ_0018534 and BTBD7 expression were significantly increased, whereas miR-153-3p expression was decreased in NSCLC tissues and cells. Circ_0018534 downregulation markedly alleviated cell proliferation, migration, invasion, and elevated cell apoptosis in NSCLC cells in vitro. MiR-153-3p inhibitors partially reversed the effects of circ_0018534 knockdown on cell proliferation, migration, invasion and apoptosis in NSCLC. Moreover, miR-153-3p could directly target BTBD7, and circ_0018534 promoted BTBD7 expression by targeting miR-153-3p. Besides, BTBD7 overexpression attenuated miR-153-3p mimics-mediated effects on NSCLC cell progression. Furthermore, circ_0018534 deletion suppressed NSCLC tumor growth in vivo.Conclusion: Our results demonstrated that circ_0018534 might contribute to the progression of NSCLC by miR-153-3p/BTBD7 axis, providing a potential target for the treatment of NSCLC.

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.

scholarly journals Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Sun ◽  
Jing Chen ◽  
Xuechao Sun ◽  
Guonian Wang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Cisplatin Sensitivity

Abstract Backgrounds As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. Methods We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. Results The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. Conclusions Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

scholarly journals MicroRNA-138 Inhibits Cell Growth, Invasion, and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop

2018 ◽  
Vol 26 (3) ◽  
pp. 385-400 ◽  
Author(s):  
Dandan Li ◽  
Changjun He ◽  
Junfeng Wang ◽  
Yanbo Wang ◽  
Jianlong Bu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

Many studies have shown that downregulation of miR-138 occurs in a variety of cancers including non-small cell lung cancer (NSCLC). However, the precise mechanisms of miR-138 in NSCLC have not been well clarified. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in NSCLC cell lines, discussing whether it could turn out to be a therapeutic biomarker of NSCLC in the future. In our study, we found that miR-138 is downregulated in NSCLC tissues and cell lines. Moreover, the low level of miR-138 was associated with increased expression of SOX4 in NSCLC tissues and cell lines. Upregulation of miR-138 significantly inhibited proliferation of NSCLC cells. In addition, invasion and EMT of NSCLC cells were suppressed by overexpression of miR-138. However, downregulation of miR-138 promoted cell growth and metastasis of NSCLC cells. Bioinformatics analysis predicted that SOX4 was a potential target gene of miR-138. Next, luciferase reporter assay confirmed that miR-138 could directly target SOX4. Consistent with the effect of miR-138, downregulation of SOX4 by siRNA inhibited proliferation, invasion, and EMT of NSCLC cells. Overexpression of SOX4 in NSCLC cells partially reversed the effect of miR-138 mimic. In addition, decreased SOX4 expression could increase the level of miR-138 via upregulation of p53. Introduction of miR-138 dramatically inhibited growth, invasion, and EMT of NSCLC cells through a SOX4/p53 feedback loop.

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