scholarly journals Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2136-2147 ◽  
Author(s):  
Haiting Gu ◽  
Junfeng Chen ◽  
Yukang Song ◽  
Haiyan Shao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Non Coding Rna

Background/Aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC). Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. The effect of GAPLINC on cell proliferation was investigated using CCK8-assay, colony formation assay, and xenograft model. The effects of GAPLINC on apoptosis and cell cycle were determined using flow cytometry. The mechanism of GAPLINC involved in NSCLC was explored using Western blot, luciferase reporter assay, and RNA fluorescence in situ hybridization. Results: We found that GAPLINC expression was up-regulated in NSCLC tissues and cell lines. Overexpression of GAPLINC was associated with poor prognosis in patients with NSCLC. Silencing of GAPLINC significantly inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G0/G1 phase. Results from xenograft transplantation showed that GAPLINC silencing inhibited the tumor growth in vivo. Interestingly, GAPLINC silencing decreased the expression of eukaryotic elongation factor-2 kinase (eEF2K) protein both in vivo and in vitro. Bioinformatic analysis and luciferase reporter confirmed that miR-661 targeted GAPLINC and eEF2K 3’-UTR and was negatively correlated with the expression of GAPLINC and eEF2K. Conclusion: Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy.

scholarly journals Circ_0005962 functions as an oncogene to aggravate non-small cell lung cancer progression via circ_0005962/miR-382-5p/PDK4 regulatory network

2020 ◽  
Author(s):  
Zhihong Zhang ◽  
Zhenxiu Shan ◽  
Rubin Chen ◽  
Xiaorong Peng ◽  
Bin Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung

AbstractNon-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs (circRNAs) were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. The expression of circ_0005962, miR-382-5p and pyruvate dehydrogenase kinase 4 (PDK4) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), PDK4, Cleaved Caspase 3 (C-caspase 3) and proliferating cell nuclear antigen (PCNA) were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. The interaction between miR-382-5p and circ_0005962 or PDK4 was predicted by the online tool CircInteractome or starbase and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft model was constructed to investigate the role of circ_0005962 in vivo. circ_0005962 expressed with a high level in NSCLC tissues and cells. Circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. MiR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. Circ_0005962 knockdown suppressed tumor growth in vivo. Circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.

scholarly journals Circ_ZFR contributes to the paclitaxel resistance and progression of non-small cell lung cancer by upregulating KPNA4 through sponging miR-195-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junmin Li ◽  
Rongmei Fan ◽  
Hui Xiao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Xenograft Model ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background A growing body of evidence has demonstrated the vital roles of circular RNAs (circRNAs) in cancer progression and drug resistance. We intended to explore the roles and mechanisms of circ_ZFR in the paclitaxel (PTX) resistance and progression of non-small cell lung cancer (NSCLC). Methods Two NSCLC cell lines A549 and H460 were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to measure the levels of circ_ZFR, ZFR, miR-195-5p and karyopherin subunit alpha 4 (KPNA4) mRNA. RNase R assay was used to analyze the characteristic of circ_ZFR. MTT assay was carried out to assess PTX resistance and cell proliferation. Flow cytometry analysis was utilized to analyze cell cycle and apoptosis. Transwell assay was used to examine cell migration and invasion. Western blot assay was conducted to measure the protein levels of Ki67, Twist1, E-cadherin and KPNA4. Dual-luciferase reporter assay was adopted to verify the combination between miR-195-5p and circ_ZFR or KPNA4. Murine xenograft model assay was used to investigate the effect of circ_ZFR on PTX resistance of NSCLC in vivo. Results Circ_ZFR level was enhanced in PTX-resistant NSCLC tissues and cells. Knockdown of circ_ZFR suppressed PTX resistance, cell cycle process, proliferation, migration and invasion and induced apoptosis in PTX-resistant NSCLC cells. For mechanism analysis, circ_ZFR knockdown markedly downregulated the expression of KPNA4 by sponging miR-195-5p, thereby promoting PTX sensitivity and suppressing cell progression in PTX-resistant NSCLC cells. In addition, circ_ZFR silencing enhanced PTX sensitivity of NSCLC in vivo. Conclusion Circ_ZFR knockdown played a positive role in overcoming PTX resistance of NSCLC via regulating miR-195-5p/KPNA4 axis, which might provide a possible circRNA-targeted therapy for NSCLC.

scholarly journals A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC)

2020 ◽  
Author(s):  
Xiang Zhu ◽  
Jing Han ◽  
Huiyin Lan ◽  
Qingren Lin ◽  
Yuezhen Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Expression Levels

Abstract Background: Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Methods: Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3’ untranslated region (3’UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues.Results: Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. Conclusions: Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

CALCR knockdown inhibits the development and progression of non-small-cell lung cancer

2021 ◽  
Author(s):  
Tao He ◽  
Feng Ling
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Expression Level ◽  
Cell Counting ◽  
Small Cell Lung

Abstract G protein-coupled receptors (GPCRs) have been reported to participant in the occurrence and development of a variety of human cancers. CALCR is one of the hundreds of GPCRs, but its expression level and functional importance have never been investigated in non-small-cell lung cancer (NSCLC). In the present study, the protein expression level of CALCR was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound healing assay and the transwell assay were performed to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed to conduct the in vivo experiments. The results indicated that the CALCR expression was abundantly up-regulated in NSCLC and positively related to tumor infiltrate. Besides, CALCR knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study verified the inhibitory effects of CALCR knockdown on NSCLC tumorigenesis. The abovementioned results provided a reference for the treatment of NSCLC, that was, CALCR knockdown might be a considerable therapeutic strategy.

scholarly journals LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yaomei He ◽  
Xiulin Jiang ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
Yixiao Yuan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Non Coding Rna ◽  
Cancerous Cell ◽  
Long Non Coding Rna

Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. Methods Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. Result Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting β-TrCP1 mediated ubiquitin degradation of β-catenin proteins, which in turn causes enhanced tumorigenesis. Conclusions Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.

scholarly journals A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC)

2020 ◽  
Author(s):  
Xiang Zhu ◽  
Jing Han ◽  
Huiyin Lan ◽  
Qingren Lin ◽  
Yuezhen Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Expression Levels

Abstract Background Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Methods Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3’ untranslated region (3’UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues. Results Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. Conclusions Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

scholarly journals Long non-coding RNA PRNCR1 modulates non-small cell lung cancer cell proliferation, apoptosis, migration, invasion, and EMT through PRNCR1/miR-126-5p/MTDH axis

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Ran Guo ◽  
Tongchen Hu ◽  
Yanheng Liu ◽  
Yinzai He ◽  
Yanling Cao
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Cell Behaviors ◽  
Non Coding Rna

Abstract Background: Non-small cell lung cancer (NSCLC) is a highly malignant tumor. Accumulating evidence suggested that prostate cancer non-coding RNA 1 (PRNCR1) participated in the pathogenesis of NSCLC, whereas the elaborate mechanism remains unclear. Hence, the role of PRNCR1 in the progression of NSCLC was investigated. Methods: Levels of PRNCR1, microRNA-126-5p (miR-126-5p), and metadherin (MTDH) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured using Cell Counting Kit-8 (CCK-8). Flow cytometry was conducted to determine cell apoptosis. Besides, transwell assay was performed to detect cell migration and invasion in NSCLC cells. The expression levels of E-cadherin, N-cadherin, Vimentin, and MTDH were detected via Western blot. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull down assays were employed to verify the relationship between miR-126-5p and PRNCR1 or MTDH. Results: PRNCR1 and MTDH levels were highly expressed, while miR-126-5p expression was lowly expressed in NSCLC tissues and cell lines. Knockdown of PRNCR1 promoted cell apoptosis, impeded proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in NSCLC cells, and these effects were abrogated by its target gene of miR-126-5p inhibitor. Moreover, MTDH as the target of PRNCR1, its overexpression reversed the impacts of miR-126-5p mimic on cell behaviors and EMT in vitro. Finally, PRNCR1 and miR-126-5p regulated MTDH expression. Conclusion: PRNCR1 modified cell behaviors and EMT via miR-126-5p/MTDH axis in NSCLC cells, providing a novel thinking for clinical treatment 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 A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC)

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiang Zhu ◽  
Jing Han ◽  
Huiyin Lan ◽  
Qingren Lin ◽  
Yuezhen Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Expression Levels

Abstract Background Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Methods Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3′ untranslated region (3’UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues. Results Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. Conclusions Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

scholarly journals Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK

2018 ◽  
Vol 45 (5) ◽  
pp. 1807-1817 ◽  
Author(s):  
Jia Shen ◽  
Banghua Wang ◽  
Tao Zhang ◽  
Ni Zhu ◽  
Zexia Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Invasion ◽  
Small Cell ◽  
Small Cell Lung

Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.

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