Long non-coding RNA MLLT4 antisense RNA 1 induces autophagy to inhibit tumorigenesis of cervical cancer through modulating the myosin-9/ATG14 axis
2
Citation
35
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract The regulatory mechanism of long non-coding RNAs (lncRNAs) in autophagy is as yet not well established. In this research, we show that the long non-coding RNA MLLT4 antisense RNA 1 (lncRNA MLLT4-AS1) is induced by the MTORC inhibitor PP242 and rapamycin in cervical cells. Overexpression of MLLT4-AS1 promotes autophagy and inhibits tumorigenesis and the migration of cervical cancer cells, whereas knockdown of MLLT4-AS1 attenuates PP242-induced autophagy. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between MLLT4-AS1 and other associated targets, such as myosin-9 and autophagy-related 14(ATG14). MLLT4-AS1 was upregulated by H3K27ac modification with PP242 treatment, and knockdown of MLLT4-AS1 reversed autophagy by modulating ATG14 expression. Mechanically, MLLT4-AS1 was associated with the myosin-9 protein, which further promoted the transcription activity of the ATG14 gene. In conclusion, we demonstrated that MLLT4-AS1 acts as a potential tumor suppressor in cervical cancer by inducing autophagy, and H3K27ac modification-induced upregulation of MLLT4-AS1 could cause autophagy by associating with myosin-9 and promoting ATG14 transcription.Keywords:
Transcription
Inducer
BAG3
ATG16L1
Cite
Citations (0)
In the last few years, accumulating evidence has indicated that numerous long noncoding RNAs (lncRNAs) are abnormally expressed in gastric cancer (GC) and are associated with the survival of GC patients. This study aimed to conduct a meta-analysis on 19 lncRNAs (AFAP1 antisense RNA 1 [AFAP1-AS1], CDKN2B antisense RNA 1 [ANRIL], cancer susceptibility 15 [CASC15], colon cancer associated transcript 2 [CCAT2], gastric adenocarcinoma associated, positive CD44 regulator, long intergenic noncoding RNA [GAPLINC], H19, imprinted maternally expressed transcript [H19], HOX transcript antisense RNA [HOTAIR], HOXA distal transcript antisense RNA [HOTTIP], long intergenic non-protein coding RNA 673 [LINC00673], metastasis-associated lung adenocarcinoma transcript 1 [MALAT1], maternally expressed 3 [MEG3], promoter of CDKN1A antisense DNA damage activated RNA [PANDAR], Pvt1 oncogene [PVT1], SOX2 overlapping transcript [Sox2ot], SPRY4 intronic transcript 1 [SPRY4-IT1], urothelial cancer associated 1 [UCA1], X inactive specific transcript [XIST], ZEB1 antisense RNA 1 [ZEB1-AS1] and ZNFX1 antisense RNA 1 [ZFAS1]) to systematically estimate their prognostic value in GC.The qualified literature was systematically searched in PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews (up to March 16, 2018), and one meta-analysis relating to the relationship between lncRNA expression and overall survival (OS) of GC patients was performed. The only evaluation criterion of survival results was OS.A total of 6,095 GC patients and 19 lncRNAs from 51 articles were included in the present study. Among the listed 19 lncRNAs, 18 lncRNAs (other than SPRY4-IT1) showed a significantly prognostic value (P<0.05).This meta-analysis suggested that the abnormally expressed lncRNAs (AFAP1-AS1, ANRIL, CASC15, CCAT2, GAPLINC, H19, HOTAIR, HOTTIP, LINC00673, MALAT1, MEG3, PANDAR, PVT1, Sox2ot, UCA1, XIST, ZEB1-AS1 and ZFAS1) were significantly associated with the survival of GC patients, among which AFAP1-AS1, CCAT2, LINC00673, PANDAR, PVT1, Sox2ot, ZEB1-AS1 and ZFAS1 were strong candidates in predicting the prognosis of GC patients.
MALAT1
Competing Endogenous RNA
Cite
Citations (50)
Cite
Citations (0)
macroautophagy 的角色(此后 autophagy ) 在癌症，到临床的干预的生物学和反应是复杂的。autophagy 是在许多肿瘤背景的 dysregulated，是清楚的，在肿瘤开始和前进期间，并且响应治疗。然而，在控制房间行为的 autophagy 的多种的机械学的角色使在一个给定的肿瘤背景预言困难 autophagy 的角色，并且，由扩展，指向 autophagy 的治疗学的结果，力量。在这评论，我们在在癌症支持 pro-tumorigenic 和 anti-tumorigenic 和 autophagy 的治疗学的角色的文学总结证据。这概述在滋养的管理，房间死亡，房间老朽， proteotoxic 应力的规定和细胞的动态平衡包含 autophagy 的角色，在在新陈代谢的变化的肿瘤主人相互作用和参予的规定。在可能的地方，我们也试着理解，为 autophagy 的这些角色的机械学的底。我们明确地阐述在在 vivo.We 使这些问题清楚些的癌症的模型也考虑 autophagy 蛋白质的任何东西或上述所有函数怎么可能是可指向的由的遗传上设计的老鼠的新兴的角色现存或 pharmacologic 代理人的未来类。我们由简短在细胞的过程为关键 autophagy 蛋白质的子集探索不在经典中的角色得出结论，并且这些怎么可能在癌症之上影响。
Cite
Citations (0)
Cite
Citations (25)
Cite
Citations (71)
Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Due to modern genomic techniques, the involvement of lncRNAs in tumorigenesis has been revealed; however, information concerning lncRNA interplay in multiple myeloma (MM) and plasma cell leukemia (PCL) is virtually absent. Herein, we aimed to identify the lncRNAs involved in MM to PCL progression. We investigated representative datasets of MM and PCL patients using next-generation sequencing. In total, 13 deregulated lncRNAs (p < 0.00025) were identified; four of them were chosen for further validation in an independent set of MM and PCL patients by RT-qPCR. The obtained results proved the significant downregulation of lymphocyte antigen antisense RNA 1 (LY86-AS1) and VIM antisense RNA 1 (VIM-AS1) in PCL compared to MM. Importantly, these two lncRNAs could be involved in the progression of MM into PCL; thus, they could serve as promising novel biomarkers of MM progression.
Plasma cell leukemia
Cite
Citations (6)
Abstract Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4‐AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4‐AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4‐AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4‐AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4‐AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4‐AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221‐3.760). In this study, a genome‐wide RNA sequencing dataset was used to identify 927 genes co‐expressing with FOXP4‐AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4‐AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome‐wide RNA sequencing dataset was done. We have found that FOXP4‐AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor‐related pathways such as NF‐kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4‐AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4‐AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome‐wide approaches, we identified the potential molecular mechanisms of FOXP4‐AS1 in PDAC and two targeted therapeutic drugs for it.
Cite
Citations (12)
Long non-coding RNAs are essential to hepatocellular carcinoma (HCC) development, progression, and incidence of drug resistance. However, the biological significance of long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) remains poorly characterized. In this study, we observed noticeable increased levels of MKLN1-AS in HCC tissues. This upregulation of MKLN1-AS was clinically associated with vascular invasion and decreased disease-free survival and overall survival of patients with HCC. Functionally, MKLN1-AS-knockdown dramatically suppressed the metastasis and growth of HCC cells in vitro and in vivo. Additionally, the knockdown of MKLN1-AS augmented the pro-apoptosis effect of lenvatinib. Taken together, our findings indicate that MKLN1-AS may be exploited as a potential prognostic predictor and therapeutic target for HCC treatment.
Cite
Citations (20)
The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.
Cite
Citations (33)