RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

Han, Sae‐Won; Kim, Hwang-Phill; Shin, Jong-Yeon; Jeong, Eun-Goo; Lee, Won‐Chul; Kim, Keon Young; Park, Sang Youn; Lee, Dae-Won; Won, Jae Kyung; Jeong, Seung‐Yong; Park, Jae-Gahb; Park, Kyu Joo; Kang, Gyeong Hoon; Seo, Jeong‐Sun; Kim, Jong‐Il; Kim, Tae-You

doi:10.1083/jcb.2047oia60

Cited by 28 publications

(33 citation statements)

References 16 publications

(20 reference statements)

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“…A-to-I RNA editing at codon 72 (Asn→Asp) of SLC22A3 may serve as an additional epigenetic mechanism relevant to esophageal cancer susceptibility. A link between A-to-I RNA editing and cancer has been established in the past few years (33)(34)(35)(36)(37)(38). Until now, only a few proteins with amino acid substitutions that are caused by a single site-specific RNA-editing event have been reported with validity, and there is no apparent causal relationship between altered RNA-editing levels and the initiation of cancer progression.…”

Section: Discussionmentioning

confidence: 99%

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer

Qin

Ming

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genomewide association study, is positively correlated with the editing level of SLC22A3. Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.RNA editing | metastasis suppressor | familial ESCC | SLC22A3 | ADAR2

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Section: Discussionmentioning

confidence: 99%

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer

Qin

Ming

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…In fact, many genes in which RNA editing occurs have been connected with multiple malignant phenotypes, and increased editing activity is associated with poor prognosis. 11 For example, RNA editing of BLCAP and FLNB functions within hepatocellular carcinoma, 21,22 RHOQ in colorectal cancer, 23 CDC14B in glioblastoma, 24 and under-editing of GluR-B in glioma. 25 Especially, AZIN1 is a well-characterized RNA editing target in liver and esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

RNA editing of AZIN1 induces the malignant progression of non-small-cell lung cancers

Chen

Shi

et al. 2017

Tumour Biol.

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RNA editing is a widespread post-transcriptional mechanism that confers specific and reproducible nucleotide changes in selected RNA transcripts and plays a critical role in many human cancers. However, little is known about how RNA editing operates in non-small-cell lung cancers. Here, we measured the sequence and expression level of genes of antizyme inhibitor 1 and adenosine deaminase acting on RNA family in 30 non-small-cell lung cancer patient samples and 13 cell lines and revealed RNA editing S367G in antizyme inhibitor 1 is a high-frequent molecular events. We determined overexpression of antizyme inhibitor 1 with RNA editing, implying the oncogenic function of this alteration. We also detected the association of adenosine deaminase acting on RNA overexpression with RNA editing occurred in antizyme inhibitor 1. Furthermore, the RNA editing could cause a cytoplasmic-to-nuclear translocation of antizyme inhibitor 1 protein and conferred the malignant phenotype of non-small-cell lung cancer cells. The in vivo experiment confirmed that this RNA editing confers higher capacity of tumor migration as well. In conclusion, antizyme inhibitor 1 RNA editing and its involvement in tumorigenesis of non-small-cell lung cancer pave a new way for potential clinical management of non-small-cell lung cancer.

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“…Computational analyses on RNA sequencing data have detected more than 2 million RNA editing sites in the human transcriptome that potentially affect a number of protein-coding genes (Ramaswami et al 2012;Bazak et al 2014;Ramaswami and Li 2014). Several studies have characterized the critical role of individual missense A-to-I RNA editing events in cancer development (Chen et al 2013;Galeano et al 2013;Han et al 2014). More recently, we and other groups have systematically characterized the RNA-editing genomic landscape in various cancer types using mRNA-seq data from The Cancer Genome Atlas (TCGA) (Fumagalli et al 2015;Han et al 2015;Paz-Yaacov et al 2015).…”

mentioning

confidence: 99%

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

et al. 2017

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RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy.

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RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

Cited by 28 publications

References 16 publications

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer

RNA editing of AZIN1 induces the malignant progression of non-small-cell lung cancers

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

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