Aberrant expression of hsa_circ_0025036 in lung adenocarcinoma and its potential roles in regulating cell proliferation and apoptosis

2018 ◽  
Vol 399 (12) ◽  
pp. 1457-1467 ◽  
Author(s):  
Shujun Wu ◽  
Hui Li ◽  
Chunya Lu ◽  
Furui Zhang ◽  
Huaqi Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Clinicopathological Parameters ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Close Link ◽  
Adenocarcinoma Cells ◽  
Proliferation And Apoptosis ◽  
Reporter Assays

AbstractAs the most common histological subtype of lung cancer, lung adenocarcinoma remains a tremendous risk to public health, which requires ceaseless efforts to elucidate the potential diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have been identified with emerging roles in tumorigenesis and development. Our preliminary work noticed that hsa_circ_0025036 was significantly upregulated in lung adenocarcinoma tissues. However, its specific roles in lung adenocarcinoma remain unclear. The results in this study revealed that hsa_circ_0025036 existed as a circular form and was aberrantly upregulated in lung adenocarcinoma tissues via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Its expression level exhibited a close link with aggressive clinicopathological parameters including cancer differentiation, TNM stage and lymph node metastasis. hsa_circ_0025036 knockdown significantly suppressed cell proliferation and promoted cell apoptosis in A549 and Calu-3 cells. Moreover, hsa_circ_0025036/miR-198/SHMT1&TGF-αaxis was identified via bioinformatics analysis and Dual-Luciferase Reporter assays. miR-198 inhibitors reversed the function of hsa_circ_0025036 knockdown. hsa_circ_0025036 knockdown exerted similar effects with miR-198 upregulation on cell proliferation and apoptosis. In conclusion, we demonstrate that hsa_circ_0025036 regulates cell proliferation and apoptosis in lung adenocarcinoma cells probably via hsa_circ_0025036/miR-198/SHMT1&TGF-αaxis. hsa_circ_0025036 may serve as a potential prognostic biomarker and a therapeutic target for lung adenocarcinoma.

scholarly journals Long non-coding RNA LINC01194 promotes the proliferation, migration and invasion of lung adenocarcinoma cells by targeting miR-641/SETD7 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fanmei Meng ◽  
Yijing Zhou ◽  
Baohua Dong ◽  
Aiqin Dong ◽  
Jingtao Zhang
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
Reporter Assays ◽  
Cancer Types ◽  
Long Non Coding Rna

Abstract Background It is increasingly evidenced that long non-coding RNAs (lncRNAs) play an important role in various diseases. LncRNA LINC01194 acts as an oncogene in several cancer types. Nevertheless, the role of LINC01194 in lung adenocarcinoma (LUAD) has not yet been revealed. Methods qRT-PCR was used to detect the expression of LINC01194, miR-641 and SETD7 mRNA, while western blot was exploited to examine SETD7 protein level. Cell proliferation was detected by colony formation and EdU assays. Transwell assays detected cell migration and invasion. TUNEL assay and flow cytometry analysis were used to detect cell apoptosis. RIP, RNA pull down and luciferase reporter assays detected the binding among LINC01194, miR-641 and SETD7. Results LINC01194 was significantly upregulated in LUAD tissues and cell lines. Knockdown of LINC01194 resulted in decreased cell proliferation, migration and invasion, and increased apoptosis. Mechanistic experiments unveiled that LINC01194 augmented SETD7 expression in LUAD cells by competitively interacting with miR-641. Rescue experiments showed that miR-641 inhibition and SETD7 overexpression rescued the repressing impacts on LUAD cell proliferation, migration and invasion caused by LINC01194 knockdown. Conclusion LINC01194 promotes the progression of LUAD by enhancing miR-641-targeted SETD7. The LINC01194/miR-641/SETD7 axis might provide new molecular targets for treating LUAD.

scholarly journals Hsa_circ_0003998 Promotes Chemoresistance via Modulation of miR-326 in Lung Adenocarcinoma Cells

2019 ◽  
Vol 27 (5) ◽  
pp. 623-628 ◽  
Author(s):  
Wanjun Yu ◽  
Weidong Peng ◽  
Hanyun Sha ◽  
Jipeng Li
Keyword(s):  
Lung Adenocarcinoma ◽  
Noncoding Rnas ◽  
Resistant Cell ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
New Class ◽  
Novel Approach ◽  
Adenocarcinoma Cells ◽  
Reporter Assays ◽  
Direct Target

Circular RNAs (circRNAs) represent a new class of noncoding RNAs that is involved in the development of cancer. However, little is known about their role in chemoresistance. In the present study, we found that hsa_circ_0003998 expression levels in lung adenocarcinoma (LAD) tissues and docetaxel-resistant cell lines (A549/DTX and H1299/DTX) were upregulated. Knockdown of hsa_circ_0003998 decreased chemoresistance, inhibited proliferation, and enhanced apoptosis in docetaxel-resistant LAD cells. Moreover, by using bioinformatics and luciferase reporter assays, we found that miR-326 was a direct target of hsa_circ_0003998. Functional analysis revealed that miR-326 mediated the effect of hsa_circ_0003998 on chemosensitivity. Our findings provide a molecular insight on understanding drug resistance in LAD cells. Therefore, inactivation of hsa_circ_0003998 or activation of miR-326 could be a novel approach for the treatment of LAD.

scholarly journals Long non-coding RNA GATA6-AS1 upregulates GATA6 to regulate the biological behaviors of lung adenocarcinoma cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Honggang Kang ◽  
Dan Ma ◽  
Jing Zhang ◽  
Jun Zhao ◽  
Mengxiang Yang
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Bioinformatic Tools ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Long Non Coding Rna

Abstract Background Lung adenocarcinoma (LUAD) is known to be one of the leading causes of cancer-related deaths globally. In recent decades, long non-coding RNAs (lncRNAs) have been indicated to exert pivotal regulating functions in multiple biological behaviors in the initiation and development of LUAD. However, the functional mechanism of lncRNA GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in LUAD has not been explored. Methods In the current study, GATA6-AS1 expression in LUAD tissues was revealed. Meanwhile, GATA6-AS1 expression in LUAD cells was investigated via RT-qPCR analysis. After A549 and H1975 cells were transfected with GATA6-AS1 overexpression plasmids, EdU and colony formation assays, TUNEL assays and flow cytometry analyses, as well as wound healing and Transwell assays were conducted to detect cell proliferation, apoptosis, migration and invasion. Afterwards, bioinformatic tools, western blot analyses, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays were performed to investigate the correlation of microRNA-4530 (miR-4530), GATA6-AS1 and GATA6. Results We found that GATA6-AS1 expression was low-expressed in LUAD tissues and cells. Furthermore, the upregulation of GATA6-AS1 suppressed the proliferative, migration and invasion abilities, as well as promoted apoptotic rate of A549 and H1975 cells. Moreover, the mechanistic investigations revealed that GATA6-AS1 upregulated the expression of its cognate sense gene GATA6 by binding with miR-4530, thereby modulating the malignant progression of LUAD cells. Conclusions GATA6-AS1 repressed LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via regulation of the miR-4530/GATA6 axis, indicating GATA6-AS1 as a new prognostic biomarker for LUAD.

LncRNA LINC00858 enhances cervical cancer cell growth through miR-3064-5p/ VMA21 axis

2021 ◽  
pp. 1-11
Author(s):  
Min Wei ◽  
Youguo Chen ◽  
Wensheng Du
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Cancer Cell Growth ◽  
Protein Coding ◽  
Gynecological Malignancy ◽  
Promising Therapeutic Target ◽  
Proliferation And Apoptosis ◽  
Reporter Assays

BACKGROUND: Cervical cancer (CC) is the most common form of gynecological malignancy. Long intergenic non-protein coding RNA 858 (LINC00858) has been identified to participate in multiple cancers. However, the role and mechanism of LINC00858 in CC cells are still elusive. AIM: The aim of this study is to explore the biological functions and mechanisms of LINC00858 in CC cells. METHODS: RT-qPCR analysis was used to examine the expression of LINC00858 in CC cells. EdU and colony formation assay were utilized to assess cell proliferation. TUNEL assay and flow cytometry assay were conducted to assess cell apoptosis. The mechanism regarding LINC00858 was certified through RNA pull down, RIP and luciferase reporter assays. RESULTS: The up-regulated LINC00858 was detected in CC cells. Reduction of LINC00858 effectively subdued CC cells proliferation and stimulated cell apoptosis. LINC00858 was determined to bind with miR-3064-5p and up-regulate VMA21 in CC cells. In rescue assays, miR-3064-5p down-regulation and VMA21 up-regulation were able to counteract the effect caused by LINC00858 decrease on CC cell proliferation and apoptosis. CONCLUSION: LINC00858 enhances cell proliferation, while restraining cell apoptosis in CC through targeting miR-3064-5p/VMA21 axis, implying that LINC00858 may serve as a promising therapeutic target for CC.

Dexmedetomidine upregulates the expression of miR-493-5p, inhibiting growth and inducing the apoptosis of lung adenocarcinoma cells by targeting RASL11B

2021 ◽  
pp. 1-8
Author(s):  
Bo Xu ◽  
Yiling Qian ◽  
Chunxiao Hu ◽  
Yongsheng Wang ◽  
Hong Gao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Adenocarcinoma Cell Line ◽  
Expression Levels ◽  
Lung Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cells ◽  
Reporter Assays ◽  
Lung Adenocarcinoma Cells ◽  
High Degree ◽  
Degree Of Similarity

Numerous studies have indicated that microRNAs (miRNAs) play critical roles in the development and progression of cancer. However, how changes to the expression levels of miRNAs in response to dexmedetomidine affects the progression of lung cancer remains poorly understood. In this study, we treated the lung adenocarcinoma cell line-A549 with dexmedetomidine and then examined the changes to the expression levels of miRNAs. We found that one of the most significantly upregulated miRNAs was miR-493-5p, which has an important role in the growth and apoptosis of lung adenocarcinoma (LUAD) cells. In addition, bioinformatics searches and luciferase reporter assays revealed that miR-493-5p targets RASL11B, which has a high degree of similarity to RAS. Finally, database searches revealed that RASL11B is associated with survival of LUAD cells. In conclusion, dexmedetomidine causes changes to the expression levels of miRNAs in LUAD, including significant upregulation of miR-493-5p. MiR-493-5p targets RASL11B, thereby inhibiting cell growth and inducing apoptosis in LUAD.

scholarly journals EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Renjie Wang ◽  
Sai Zhang ◽  
Xuyi Chen ◽  
Nan Li ◽  
Jianwei Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioblastoma Multiforme ◽  
Aurora Kinase ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Reporter Assays

Abstract Background Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). Methods A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. Results In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. Conclusions Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM. Graphical abstract

scholarly journals CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis

2019 ◽  
Author(s):  
Haote Liang ◽  
Hang Huang ◽  
Yeping Li ◽  
Yongyong Lu ◽  
Tingyu Ye
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Tumorigenesis And Progression ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Proliferation And Invasion

Abstract Emerging evidences have uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared to adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could be act as a new biomarker and further developed to be a therapeutic target in BC.

scholarly journals CircRNA 0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis

2019 ◽  
Author(s):  
Haote Liang ◽  
Hang Huang ◽  
Yeping Li ◽  
Yongyong Lu ◽  
Tingyu Ye
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Tumorigenesis And Progression ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Proliferation And Invasion

Abstract Emerging evidences have uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared to adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could be act as a new biomarker and further developed to be a therapeutic target in BC.

scholarly journals The tsRNAs (tRFdb-3013a And tRFdb-3013b) Serve As Novel Biomarkers For Colon Adenocarcinomas

2021 ◽  
Author(s):  
Xiaoling Wu ◽  
Lihong Tan ◽  
Zhurong Tang ◽  
Chunjie Wen ◽  
Huan Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Colon Adenocarcinoma ◽  
Bioinformatic Analysis ◽  
Molecular Signature ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Diagnosis And Prognosis ◽  
Adenocarcinoma Cells ◽  
Reporter Assays ◽  
Novel Biomarkers

Abstract Background: The tsRNAs (tRNA-derived small RNAs) are novel class of small non-coding RNAs derived from transfer-RNAs. Colon adenocarcinoma (COAD) are well known malignant intestinal tumors. This study focused on the identification and characterization of tsRNA biomarkers in colon adenocarcinomas. Methods: Data processing, bioinformatic analysis and visualization were performed with R or Python software. The cell proliferation, migration and invasion ability were described by CCK-8 and transwell assays. Luciferase reporter assays were performed to test the binding of tsRNA with its target.Results: With computational approaches, we identified the tsRNA fragments profiles within COAD datasets, and discriminated forty-two differentially expressed tsRNAs between colon adenocarcinomas and non-tumor controls. Among the fragments derived from the 3′ end of mature tRNA-His-GUG (a histidyl-transfer-RNA), tRFdb-3013a and tRFdb-3013b (tRFdb-3013a/b) were significantly decreased in colon adenocarcinomas, especially, tRFdb-3013a/b may tend to down-regulated in the patients with lymphatic or vascular invasion present. The clinical survival of colon adenocarcinomas patients with low tRFdb-3013a/b expression was significantly worse than that of high expression patients. In colon adenocarcinoma cells, tRFdb-3013a could suppressed cell proliferation, and reduced cell migration and invasion ability. The enrichment analyses showed that most of tRFdb-3013a-related genes were enriched in the extracellular matrix associated GO terms, phagosome pathway, and a GSEA molecular signature. Mechanically, the 3′UTR of ST3GAL1 mRNA was predicted to contain the putative binding sites of tRFdb-3013a/b, tRFdb-3013a/b might directly target ST3GAL1 and regulate ST3GAL1 expression in colon adenocarcinomas. Conclusions: These results suggested that tRFdb-3013a and tRFdb-3013b might serve as novel biomarkers for diagnosis and prognosis of colon adenocarcinomas, and play an important role in tumor progression of colon adenocarcinomas.

Long Non-Coding RNA GATA6-AS1 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Through Sponging miR-331-3p and Regulating SOCS1/JAK2/STAT3 Pathway

2020 ◽  
Author(s):  
Xiaodong Huo ◽  
Huixing Wang ◽  
Ning Jiang ◽  
Kuo Yang ◽  
Bin Huo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Stat3 Signaling ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Stat3 Signaling Pathway ◽  
Reporter Assays ◽  
Long Non Coding Rna

Abstract Background: Accumulating evidence has indicated the remarkable roles of long non-coding RNAs (lncRNAs) as oncogenes or tumor suppressors in many malignancies. The involvement of lncRNA GATA6-AS1 in cancers remains largely undiscovered. Herein, our research was aimed at elucidating the function and mechanism of GATA6-AS1 in lung adenocarcinoma (LUAD).Methods: Gene expression was measured through qRT-PCR and WB. Cell proliferation ratio was determined using CCK-8 and EdU assays. Cell apoptosis ratio was determined using TUNEL and flow cytometry assays. Molecular interactions were examined through RIP, RNA pull-down and luciferase reporter assays.Results: GATA6-AS1 expression was markedly down-regulated in LUAD cell lines. GATA6-AS1 could inhibit LUAD cell proliferation and promote cell apoptosis. Mechanistically, GATA6-AS1 was identified as the molecular sponge for miR-331-3p, whose knockdown in LUAD cells could reinforce the tumor-suppressing effects of GATA6-AS1 overexpression. Moreover, GATA6-AS1 functions as a competing endogenous RNA (ceRNA) through sequestering miR-331-3p to deregulate SOCS1, thus inhibiting JAK2/STAT3 signaling pathway and suppressing LUAD cell viability.Conclusions: These results demonstrate the tumor-suppressing function and mechanism of lncRNA GATA6-AS1 in LUAD cells. The axis of GATA6-AS1/miR-331-3p/SOCS1/JAK2/STAT3 can be adopted as a novel approach for LUAD treatment.

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