Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer

Zhu, Liyuan; Zhu, Yuanxun; Han, Shuting; Chen, Miaoqin; Song, Ping; Dai, Dongjun; Xu, Wenxia; Jiang, Tingting; Feng, Lifeng; Shin, Vivian Y.; Wang, Xian; Jin, Hongchuan

doi:10.1038/s41419-019-1585-2

Cited by 153 publications

(148 citation statements)

References 58 publications

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“…METTL3 is a predominant MTase for m 6 A modification, and its underlying mechanism must be complex, involving multiple molecules and pathways. The lncRNA ARHGAP5-AS1, miR-600, miRNA let-7g, and miR-33a can influence human cancer progression by targeting METTL3 (35,36,52,53). Conversely, METTL3 can promote pri-miRNA processing by interacting with DGCR8 (2,20,54).…”

Section: Discussion and Outlookmentioning

confidence: 99%

“…Its expression level gradually increased with the increasing tumor stage and grade. METTL3 was an indicator of poor prognosis and METTL3 silencing inhibited the proliferation, migration, and invasion abilities of cells, colony formation, and motility (24,(47)(48)(49)(50)(51)(52), demonstrating that METTL3 plays an oncogenic role in these cancers. Taketo et al reported that a METTL3-knockdown pancreatic cancer cell line showed higher sensitivity to anticancer agents such as gemcitabine, 5-fluorouracil, cisplatin, and irradiation, suggesting that METTL3 is a potential target for the enhancement of therapeutic efficacy (25).…”

Section: Mettl3 In Other Cancersmentioning

confidence: 99%

“…Wei et al showed that miR-600 can reverse the effect of METTL3 overexpression, as well as overexpression of the related genes in the PI3K/AKT and βcatenin/stat3 signaling pathways (36). The lncRNA ARHGAP5-AS1 can stimulate m 6 A modification of ARHGAP5 mRNA to stabilize ARHGAP5 mRNA, which is upregulated in gastric cancer, in the cytoplasm to promote chemoresistance by recruiting METTL3 (52). Hepatitis B X-interacting protein (HBXIP) upregulates METTL3 in breast cancer cells by inhibiting the miRNA let-7g, which downregulates the expression of METTL3 by targeting its 3 ′ UTR.…”

Section: Regulatory Mechanisms Of Mettl3mentioning

confidence: 99%

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Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

et al. 2019

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Methyltransferase-like 3 (METTL3), a predominantly catalytic enzyme in the N 6 -methyladenosine (m 6 A) methyltransferase system, is dysregulated and plays a dual role (oncogene or tumor suppressor) in different human cancers. The expression and pro-or anticancer role of METTL3 in different cancers remain controversial. METTL3 is implicated in many aspects of tumor progression, including tumorigenesis, proliferation, invasion, migration, cell cycle, differentiation, and viability. Most underlying mechanisms involve multiple signaling pathways that rely on m 6 A-dependent modification. However, METTL3 can also modulate the cancer process by directly promoting the translation of oncogenes via interaction with the translation initiation machinery through recruitment of eukaryotic translation initiation factor 3 subunit h (eIF3h). In this review, we summarized the current evidence on METTL3 in diverse human malignancies and its potential as a prognostic/ therapeutic target.

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Section: Discussion and Outlookmentioning

confidence: 99%

Section: Mettl3 In Other Cancersmentioning

confidence: 99%

Section: Regulatory Mechanisms Of Mettl3mentioning

confidence: 99%

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Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

et al. 2019

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“…Ultimately, ARHGAP5-AS1 enhanced the expression of its target gene ARHGAP5 and promoted chemoresistance in gastric cancer cells. Therefore, targeting the ARHGAP5-AS1/ARHGAP5 axis might serve as a potential therapeutic strategy to overcome chemoresistance in gastric cancer [107].…”

Section: Regulation Of M6a Modifications By Noncoding Rnasmentioning

confidence: 99%

The interplay between m6A RNA methylation and noncoding RNA in cancer

et al. 2019

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N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. It also regulates cell proliferation and metastasis, stem cell differentiation, and homeostasis in cancer by affecting the biological function of cells. Interestingly, noncoding RNAs also play significant roles in regulating these m6A modifications. Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.

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“…In recent years, the relationship between long non-coding RNA (lncRNA) and autophagy has several breaks in the diagnosis, treatment, and prognosis of GC. Pieces of evidence showed that lncRNA is vital for the occurrence, prognosis, and chemoresistance of GC by regulating autophagy-related mRNA [24][25][26]. Some studies have demonstrated that silencing of LINC01419 and CCAT2 promotes autophagy through constraining the PI3K/Akt1/mTOR pathway thus inhibiting the invasion and migration of GC cells [27,28]; Another study also revealed that autophagy was associated with the proliferation of GC cells, partially due to the MALAT1 promoted by downregulating miR-204 [29].…”

Section: Introductionmentioning

confidence: 99%

Prognostic model based on autophagy-related lncRNAs in gastric cancer

Cheng¹,

Cao²,

Chen³

2020

Preprint

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Background: Gastric cancer (GC) is one of the most pravelent cancer in the world. Although increasing studies have indicated that autophagy-related long non-coding RNA (lncRNA) plays an essential role in the occurrence of GC, the prognosis of GC based on autophagy is still deficient.Method: Autophagy-related lncRNAs were obtained by using the correlation test with the autophagy-related gene. Data was downloaded from The Cancer Genome of Atlas stomach adenocarcinoma (TCGA-STAD) dataset. The prognostic autophagy-related lncRNAs significantly correlated with survival of TCGA-STAD dataset were obtained by using Kaplan-Meier and univariate Cox regression analysis. TCGA-STAD dataset was separated into a training set and a testing set randomly. The model was constructed based on the training set through the least absolute shrinkage and selection operator (LASSO) regression. The testing set and TCGA-STAD were used to validate the accuracy of the model. Every patient got a risk score (RS) and patients were separate into high-risk group and low-risk group due to the median RS. The prognostic network was built and the mRNAs in the system were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The signaling pathways that the differentially expressed genes (DEGs) between two types of risk group mainly participated in were distinguished through Gene Set Enrichment Analysis (GSEA). The individual’s survival rate was predicted through the nomogram.Results: 24 autophagy-related lncRNAs were found strongly associated with the survival of the TCGA-STAD dataset. Among them, 11 lncRNAs were selected to build the risk score model through LASSO regression. The multivariate Cox analysis showed that the RS could be an independent prognosis predictor. The Kaplan-Meier survival analysis and the Receiver Operating Characteristic (ROC) curve indicated the model had an excellent prediction effect. GO, and KEGG analysis revealed that the mRNAs in the prognostic network were mainly involved in the autophagy and ubiquitin-like protein ligase binding. GSEA analysis uncovered that the DEGs in high-risk group partially participated in the ECM receptor interaction and other signaling pathways.Conclusions: Our results indicated that the risk score model based on the autophagy-related lncRNAs performed well in the prediction of prognosis for patients with GC.

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Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer

Cited by 153 publications

References 58 publications

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

The interplay between m6A RNA methylation and noncoding RNA in cancer

Prognostic model based on autophagy-related lncRNAs in gastric cancer

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