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 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 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.

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 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.

scholarly journals Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Kaili Long ◽  
Lili Gu ◽  
Lulu Li ◽  
Ziyu Zhang ◽  
Enjie Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Molecular Compound ◽  
Small Cell Lung

AbstractApurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.

scholarly journals Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Ning Liu ◽  
Weijing Wu ◽  
Zhixing Zhu ◽  
Yuan Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Immune Infiltration

Abstract Background Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated. Methods We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR. Results The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC. Conclusions The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.

scholarly journals Expression Profiles of microRNAs in Drug-Resistant Non-Small Cell Lung Cancer Cell Lines Using microRNA Sequencing

2018 ◽  
Vol 51 (6) ◽  
pp. 2509-2522 ◽  
Author(s):  
Shousen Hu ◽  
Yongliang Yuan ◽  
Zhizhen Song ◽  
Dan Yan ◽  
Xiangzhen Kong
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Nsclc Cell ◽  
Drug Resistant ◽  
Small Cell Lung

Background/Aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines. Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Results: A total of 29 upregulated miRNAs and 36 downregulated miRNAs were found in the drug-resistant NSCLC cell lines, of which 26 upregulated and 36 downregulated miRNAs were found to be involved in the Ras signaling pathway. The expression levels, survival analysis, and receiver operating characteristic curve of the dysregulated miRNAs based on The Cancer Genome Atlas database for lung adenocarcinoma showed that hsa-mir-192, hsa-mir-1293, hsa-mir-194, hsa-mir-561, hsa-mir-205, hsa-mir-30a, and hsa-mir-30c were related to lung cancer, whereas only hsa-mir-1293 and hsa-mir-561 were not involved in drug resistance. Conclusion: The results of this study may provide novel biomarkers for drug resistance in NSCLC and potential therapies for overcoming drug resistance, and may also reveal the potential mechanisms underlying drug resistance in this disease.

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.

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