Long non-coding RNA LINC01116 is overexpressed in lung adenocarcinoma and promotes tumor proliferation and metastasis.
Ontology highlight
ABSTRACT:
SUBMITTER: Zeng L
PROVIDER: S-EPMC7476163 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma. Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung adenocarcinoma tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with TNM stage, tumor size, and lymph node metastasis. The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup. Moreover, HNF1A-AS1 was determined to promote tumor proliferation and metastasis, both in vitro and in vivo, by regulating cyclin D1, E-cadherin, N-cadherin and ?-catenin expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.
| S-EPMC4496209 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been involved in the process of cancer occurrence, progression, and treatment. Lung cancer-related lncRNAs are still an emerging field, thus we sought to identify novel functional lncRNAs as candidate targets in lung cancer. Here, we identified one novel lncRNA, MUC5B-AS1 (Ensembl: ENST00000532061.2). MUC5B-AS1 was upregulated in lung adenocarcinoma tissues compared with normal lung tissues. Moreover, MUC5B-AS1 promoted lung cancer cell migration and invasion in vitro and promoted lung cancer cell metastasis in vivo. MUC5B-AS1 and its cognate sense transcript MUC5B were highly co-expressed and mutually regulated in lung adenocarcinoma. Mechanistically, MUC5B-AS1 promoted cell migration and invasion by forming an RNA-RNA duplex with MUC5B, thereby increasing MUC5B expression levels in lung adenocarcinoma. The high expression of MUC5B was significantly associated with poor outcomes in lung adenocarcinoma. Our findings highlight MUC5B-AS1 functions as an oncogenic lncRNA in tumor metastasis and implicate MUC5B-AS1 as an attractive candidate target for lung adenocarcinoma treatment.
| S-EPMC5906460 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LAD) is one of the most frequently diagnosed pathological categories of human lung cancer. Nevertheless, the link between long non-coding RNA (lncRNA) LINC01116 and LAD remains poorly investigated.MethodsQRT-PCR and western blot were applied for quantifying the expression of RNAs and proteins. Both functional experiments assays in vitro and xenografts model in vivo were implemented for analyzing LINC01116 function in LAD while molecular relationship among RNAs was investigated via mechanism experiments.ResultsLINC01116 was expressed at an abnormally high level in LAD, which was induced by transcription activator EGR1. LINC01116 depletion restrained proliferation, migration and invasion, yet facilitated apoptosis of LAD cells. MiR-744-5p could bind to LINC01116. MiR-744-5p inhibitor reversed the inhibitory effects of silencing LINC01116 on LAD malignant behaviors. In addition, cell division cycle-associated protein 4 (CDCA4) shared binding sites with miR-744-5p. Silencing LINC01116 elicited decline in CDCA4 mRNA and protein levels. Moreover, CDCA4 up-regulation could counteract the biological effects of LINC01116 knockdown on LAD cells.ConclusionOur data revealed that LINC01116 promoted malignant behaviors of LAD cells by targeting miR-744-5p/CDCA4 axis, implying the theoretical potential of LINC01116 as a novel target for LAD treatment.
| S-EPMC8180037 | biostudies-literature
Project description:Introduction: Transforming growth factor-beta (TGFβ) signaling plays a vital role in lung adenocarcinoma (LUAD) progression. However, the involvement of TGFβ-regulated long non-coding RNAs (lncRNAs) in metastasis of LUAD remains poorly understood. Methods: We performed bioinformatic analyses to identify putative lncRNAs regulated by TGF-β/SMAD3 and validated the results by quantitative PCR in LUAD cells. We performed luciferase reporter and chromatin immunoprecipitation assays to demonstrate the transcriptional regulation of the lncRNA histocompatibility leukocyte antigen complex P5 (HCP5) we decided to focus on. Stable HCP5 knockdown and HCP5-overexpressing A549 cell variants were generated respectively, to study HCP5 function and understand its mechanism of action. We also confirmed our findings in mouse xenografts and metastasis models. We analyzed the correlation between the level of lncRNA expression with EGFR, KRAS mutations, smoke state and prognostic of LUAD patients. Results: We found that the lncRNA HCP5 is induced by TGFβ and transcriptionally regulated by SMAD3, which promotes LUAD tumor growth and metastasis. Moreover, HCP5 is overexpressed in tumor tissues of patients with LUAD, specifically in patients with EGFR and KRAS mutations and current smoker. HCP5 high expression level is positively correlated with poor prognosis of patients with LUAD. Finally, we demonstrated that upregulation of HCP5 increases the expression of Snail and Slug by sponging the microRNA-203 (miR-203) and promoting epithelial-mesenchymal transition (EMT) in LUAD cells. Conclusions: Our work demonstrates that the lncRNA HCP5 is transcriptionally regulated by SMAD3 and acts as a new regulator in the TGFβ/SMAD signaling pathway. Therefore, HCP5 can serve as a potential therapeutic target in LUAD.
| S-EPMC6525996 | biostudies-literature
Project description:Background:Various evidences showed that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of malignancies. However, the exact role and regulatory mechanism of lncRNA TP73-AS1 in the pathogenesis and progression of lung adenocarcinoma remain to be further elucidated. Purpose:The aim of this study was to investigate the functional role and underlying mechanism of lncRNA TP73-AS1 in lung adenocarcinoma progression. Methods:RT-PCR assay was employed to detect TP73-AS1 expression in lung adenocarcinoma tissues and cells. The function of TP73-AS1 in lung adenocarcinoma progression was estimated by MTT assay, EdU assay, flow cytometry, Western blot, wound-healing assay and transwell assay. Results:LncRNA TP73-AS1 expression was significantly increased in lung adenocarcinoma tissues and cell lines. Moreover, functional assays revealed that silencing of lncRNA TP73-AS1 could attenuate cell proliferation, migration, invasion and epithelial-mesenchymal transition of lung adenocarcinoma, while enhanced expression of lncRNA TP73-AS1 led to the opposite results. Additionally, lncRNA TP73-AS1 knockdown could facilitate cell apoptosis and overexpression of lncRNA TP73-AS1 inhibited cell apoptosis. In addition, we further determined that lncRNA TP73-AS1 regulated cell metastasis through inducing the activation of Wnt/?-catenin signaling pathway in lung adenocarcinoma. Conclusion:Our results indicated that lncRNA TP73-AS1 may play an oncogenic role in lung adenocarcinoma progression, which provided a promising therapy strategy for the treatment of lung adenocarcinoma.
| S-EPMC6859124 | biostudies-literature
Project description:BackgroundLong non-coding RNA SPRY4 intronic transcript 1 (Lnc RNA SPRY4-IT1) was aberrant-expressed in various kinds of cancer. Increasing evidence demonstrated that lnc RNAs involved in tumorigenesis and metastasis. In this study, we aimed to explore the biological role of SPRY4-IT1 on the phenotype of nasopharyngeal carcinoma (NPC) in vitro and in vivo.MethodsThe expression level of SPRY4-IT1 in NPC cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and colony formation assay were used to detect cell proliferation. Wound-healing assay, transwell assay and animal experiment were performed to evaluate the ability of cell migration and metastasis. Cell cycle distribution and apoptosis were determined by flow cytometry. Western blotting and immunofluorescence were employed to identify protein expression.ResultsSPRY4-IT1 was significantly up-regulated in several NPC cell lines (6-10B, CNE-2, and HONE-1) compared with human immortalized nasopharyngeal epithelial cell (NP69). Silencing of SPRY4-IT1 inhibited proliferation, migration, and metastasis, and induced significant G2/M phase arrest and apoptosis. Western blotting showed that the expression levels of cell cycle-related proteins (cyclin B1, cdc2 and p-cdc2) were down-regulated and apoptosis-associated proteins (PARP, cleaved PARP and cleaved caspase-3) were up-regulated after knockdown of SPRY4-IT1. The expression level of E-cadherin was increased and the expression of Vimentin, Snail and Twist1 were decreased after the SPRY4-IT1 knockdown.ConclusionlncRNA SPRY4-IT1 played a significant role in NPC proliferation, migration and metastasis, suggesting that SPRY4-IT1 might be a potential therapeutic target for the treatment of NPC.
| S-EPMC8976472 | biostudies-literature
Project description:BackgroundWe have previously developed a unique metastasis-associated signature consisting of six long non-coding RNAs (lncRNAs), including a novel lncRNA, namely LINC02323. In the present study, we aimed to investigate the underlying roles of LINC02323 in the migration, invasion and TGF-β-induced epithelial-mesenchymal transition (EMT) of lung adenocarcinoma (LUAD) cells.MethodsThe distribution of LINC02323 was detected by the nuclear-plasma separation experiment. Cell proliferation was assessd by MTT assay, and cell migration and invation were detected by transwell assays. EMT was detected by RT-qPCR and western blotting. Interaction between miRNA and LINC02323 was predicted by starBase v2.0 and confirmed by the double luciferase reporting system.ResultsLINC02323 was distributed in the cytoplasm and nucleus. The overexpression or deletion of LINC02323 did not affect the proliferation of LUAD cells, while significantly affected the migration and invasion of LUAD cells. TGF-β-induced EMT process was significantly affected by both RNA interference (RNAi) and overexpression of LINC02323. The predicted results showed that there were binding sites between LINC02323 and miR-1343-3p. The expression of LINC02323 was found to be negatively correlated with miR-1343-3p in LUAD by analyzing The Cancer Genome Atlas (TCGA) database. The double luciferase reporting system, RT-qPCR and western blotting experiments confirmed that LINC02323 could bind to miR-1343-3p, which bound to TGF-β receptor 1 (TGFBR1). Inhibition of miR-1343-3p reversed LINC02323 silencing-mediated suppression of migration, invasion and EMT.ConclusionsLINC02323 acts as a competing endogenous RNA (ceRNA), which sponged miR-1343-3p to upregulate the TGFBR1 expression and promote the EMT and metastasis in LUAD.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: LINC02323 promotes epithelial-mesenchymal transition and metastasis via sponging miR-1343-3p in lung adenocarcinoma.What this study addsLINC02323 is a key molecule in the process of invasion and metastasis of LUAD and might be used as a potential target in metastatic cancer.
| S-EPMC7471025 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been investigated in human carcinogenesis. The lncRNA BX357664 has emerged as a novel lncRNA that was initially recognized by a microarray analysis. The present study aimed to identify the expression and functional roles of lncRNA BX357664 in lung cancer. The transcription level of BX357664 was initially revealed to be downregulated in clinical lung cancer tissues and in a series of lung cancer cell lines. Clinical data demonstrated that the high expression of BX357664 was associated with tumor size, distant metastasis and Tumor-Node-Metastasis stage. Following the overexpression of BX357664 in A549 and 95D cells, the potential of cells to form colonies, as well as the proliferation and motility abilities, were revealed to be decreased. Furthermore, the cell cycle was arrested in the G0/G1 phase by BX357664 modulation. Transwell analysis and a wound-healing assay also demonstrated that overexpression of BX357664 in A549 and 95D cells significantly inhibited cell migration and invasion. These data suggested that BX357664 inhibits cell proliferation and metastasis in lung cancer. The results of the present study provided evidence that BX357664 is a novel lncRNA that may aid in the diagnosis and treatment of lung cancer.
| S-EPMC6365958 | biostudies-literature
Project description:Long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) plays a critical role in progression of several cancers. In this study, lncRNA-ATB was significantly up-regulated in NSCLC tissues and cell lines, and high lncRNA-ATB expression indicated poor prognosis. Knockdown of lncRNA-ATB suppressed NSCLC cell growth, colony formation, migration, invasion and reversed epithelial-mesenchymal transition. In vivo study showed that silencing lncRNA-ATB inhibited tumor growth. Further mechanism studies demonstrated that lncRNA-ATB was a target of miR-141-3p. MiR-141-3p expression was negatively related to lncRNA-ATB expression in NSCLC tissues. These results suggested that inhibiting lncRNA-ATB might be an approach for NSCLC treatment.
| S-EPMC7039450 | biostudies-literature
Project description:BackgroundIt 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.MethodsqRT-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.ResultsLINC01194 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.ConclusionLINC01194 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.
| S-EPMC7722326 | biostudies-literature