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 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 CD151 drives cancer progression depending on integrin α3β1 through EGFR signaling in non-small cell lung cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jianjie Zhu ◽  
Tingting Cai ◽  
Jieqi Zhou ◽  
Wenwen Du ◽  
Yuanyuan Zeng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Tumor Proliferation ◽  
Small Cell Lung

Abstract Background Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion. Methods First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied. Results High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs. Conclusions Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment.

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 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.

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 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.

scholarly journals Upregulation of microRNA-483-5p Advances Non-small Cell Lung Cancer (NSCLC) Progression via Stifling HIPK2 Expression

2021 ◽  
Author(s):  
Lingyun Dong ◽  
Jiangnan Zheng ◽  
Zhiyu Bai ◽  
Yanfang Lu ◽  
Weizhen Song ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Incidence And Mortality

Abstract Background: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer and has a high incidence and mortality rate. The combination of radiotherapy and chemotherapy is used widely to treat locally advanced NSCLC, but the clinical efficacy is limited. MiRNA-483-5p has been connected to the improvement of an assortment of malignancies. Notwithstanding, its capacity in NSCLC stays obscure. Methods: Here we utilized benefit- or loss-of-miRNA-483-5p expression to investigate the effect of miRNA-483-5p on NSCLC. Results: The results showed that MiRNA-483-5p is entirely up-regulated in NSCLC tissues and cell lines. MiRNA-483-5p inhibitor blocked cell viability, proliferation, migration, invasion but promoted apoptosis, suggesting miRNA-483-5p acts as an oncogene in NSCLC. TargetScan predicted that HIPK2 was an objective gene of miRNA-483-5p. Then, luciferase reporter assay further confirmed that miRNA-483-5p specifically attacked HIPK2’s 3’UTR, suggesting the targeted relationship between miRNA-483-5p and HIPK2. Moreover, HIPK2 acted as a redox signal modulator and was associated with a variety of malignant tumors. The current examination affirmed the low HIPK2 expression in the NSCLC tissues and cell lines. Moreover, overexpression of HIPK2 inhibited NSCLC cell viability, proliferation, migration, invasion, but enhanced apoptosis. More importantly, co-transfection with HIPK2 and miRNA-483-5p reversed these effects, suggesting that miRNA-483-5p facilitated tumor progression by inhibiting HIPK2. Conclusions: Hence, our findings indicated that miRNA-483-5p might be a promising remedial target in NSCLC and give major premise to clinical therapeutics.

scholarly journals MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Haiping Xiao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Metastasis ◽  
Underlying Mechanism ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Distant metastasis is thought to be one of the most important factors responsible for the failure of NSCLC therapy. MicroRNA-7-5p (miR-7-5p) has been demonstrated to be a tumor suppressor in breast cancer, hepatocarcinoma, prostate cancer and glioblastoma multiforme (GBM). However, its role in NSCLC is still not fully understood. This study evaluated the role of miR-7-5p in the progression of NSCLC and explored the underlying mechanism. Materials & methods The quantitative real-time PCR (qPCR), MTT, migration and invasion assays were used to evaluate the effects of miR-7-5p on the proliferation, migration and invasion of A549 and SPCA-1 cells. A tumor xenograft model was created to determine the effects of miR-7-5p on metastasis in vivo. The dual-luciferase reporter gene, neuro-oncological ventral antigen 2 (NOVA2) overexpression and western blotting assays were performed to explore the underlying mechanism. Results MiR-7-5p is downregulated in NSCLC tissues and lung cancer cell lines. It suppresses proliferation, migration, invasion and EMT marker expression in vitro and in vivo. Further study showed that miR-7-5p suppresses tumor metastasis of NSCLC by targeting NOVA2. Overexpression of NOVA2 attenuates the miR-7-5p-mediated inhibitory effect on lung cancer cells. Conclusion MiR-7-5p suppresses NSCLC metastasis. Targeting miR-7-5p may contribute to the success of NSCLC therapy.

FOXD3-AS1 suppresses the progression of non-small cell lung cancer by regulating miR-150/SRCIN1axis

2020 ◽  
Vol 29 (3) ◽  
pp. 417-427 ◽  
Author(s):  
Tao Ji ◽  
Yanan Zhang ◽  
Zheng Wang ◽  
Zuoxu Hou ◽  
Xuhui Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Gene Assay ◽  
Proliferation And Invasion

BACKGROUND: Long non-coding RNA (lncNRA) forkhead box D3 antisense RNA 1 (FOXD3-AS1) has been proved to promote or suppress the occurrence and development of multiple types of human tumors. However, the function and mechanism of FOXD3-AS1 in non-small cell lung cancer (NSCLC) are scarcely understood. METHODS: qRT-PCR was used for detecting FOXD3-AS1, miR-150 and SRC kinase signaling inhibitor 1 (SRCIN1) mRNA expression in NSCLC tissues, and the relationship between pathological characteristics of NSCLC patients and FOXD3-AS1 expression level was analyzed. With human NSCLC cell lines H1299 and A549 as cell models, CCK-8 and BrdU assays were employed for detecting cancer cell proliferation, and Transwell assay was employed for detecting cell invasion ability. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used for the verification of the targeting relationshipe between FOXD3-AS1 and miR-150, and Western blot was employed for detecting SRCIN1 protein expression. RESULTS: FOXD3-AS1 expression was significantly reduced in NSCLC tissues and cell lines, and low expression of FOXD3-AS1 was closely related to positive lymph node metastasis and relatively high tumor grade. FOXD3-AS1 over-expression inhibited the proliferation and invasion of H1299 cell lines, while its knockdown promoted the proliferation and invasion of A549 cells. Additionally, it was confirmed that FOXD3-AS1 suppressed the expression of miR-150 by targeting it, and up-regulated the expression of SRCIN1. CONCLUSIONS: FOXD3-AS1 indirectly enhances the expression of SRCIN1 by targeting miR-150, thereby inhibiting NSCLC progression.

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