Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma

Fu, Ting‐Ying; Wu, Ching-Kuan; Sie, Huei-Cin; Cheng, Jiin‐Tsuey; Lin, Yaoh‐Shiang; Liou, Horng-Huei; Tseng, Yu-Kai; Shu, Chih‐Wen; Yen, Leing-Ming; Tseng, Hui‐Wen; Tseng, Ching‐Jiunn; Ger, Luo‐Ping; Liu, Pei‐Feng

doi:10.18632/oncotarget.13197

Cited by 31 publications

(31 citation statements)

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“…Although our focus here was LFNG, many of the other genes we discovered in our analysis may also regulate melanoma metastasis. For example, the DEXD/H box helicase 60 ( DDX60 ) gene, a known regulator of the antiviral response and a DNA‐/RNA‐binding protein, has been reported to be associated with the development and prognosis of squamous cell carcinoma (Fu et al ., ). Similarly, PTK2B has been reported to be involved in the CCR7‐mediated regulation of metastasis in squamous cell carcinoma (Yue et al ., ) and was found to be downregulated in our study.…”

Section: Discussionsupporting

confidence: 65%

Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

et al. 2018

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Metastasis is the leading cause of death in patients with advanced melanoma, yet the somatic alterations that aid tumour cell dissemination and colonisation are poorly understood. Here, we deploy comparative genomics to identify and validate clinically relevant drivers of melanoma metastasis. To do this, we identified a set of 976 genes whose expression level was associated with a poor outcome in patients from two large melanoma cohorts. Next, we characterised the genomes and transcriptomes of mouse melanoma cell lines defined as weakly metastatic, and their highly metastatic derivatives. By comparing expression data between species, we identified lunatic fringe (LFNG), among 28 genes whose expression level is predictive of poor prognosis and whose altered expression is associated with a prometastatic phenotype in mouse melanoma cells. CRISPR/Cas9‐mediated knockout of Lfng dramatically enhanced the capability of weakly metastatic melanoma cells to metastasise in vivo, a phenotype that could be rescued with the Lfng cDNA. Notably, genomic alterations disrupting LFNG are found exclusively in human metastatic melanomas sequenced as part of The Cancer Genome Atlas. Using comparative genomics, we show that LFNG expression plays a functional role in regulating melanoma metastasis.

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Section: Discussionsupporting

confidence: 65%

Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

et al. 2018

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“…However, studies have shown that AIM2 inhibits the occurrence of CRC by regulating intestinal epithelial cells via an inflammasome-independent manner [ [28]. Therefore, we hypothesize that DNA sensors may play important roles in the development of colitis and CRC.…”

Section: Introductionmentioning

confidence: 92%

DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease

He¹,

Liu²,

Lai³

et al. 2020

J. Cancer

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Background: DNA sensors are innate immune receptors that detect intracellular endogenous or exogenous DNA. They are critical to trigger immune response against DNA viral and intracellular bacterial infection, and are involved in inflammatory diseases and tumorigenesis. Recent accumulating evidences indicated that DNA sensors are also crucial for controlling the development of colorectal cancer (CRC). However, a systematic study on the expression profile of DNA sensors in CRC and their clinical significance are still lacking. Methods: We investigated the expression profile of DNA sensors in CRC and their clinical significance by taking advantage of clinical CRC samples, mouse AOM/DSS treatment model, and Oncomine ® bioinformatics platform. Results: Our study identified that the expression of DNA sensors, including AIM2, DAI, as well as inflammasome molecules ASC/IL-18, TLR9 and adaptor MyD88, and DDX60 decreased in human CRC, whereas the expression of DHX9, DHX36, and DDX41 significantly increased. Among them, the expression of AIM2/ASC/IL-18, MyD88, DAI, DHX36, and DDX60 were associated with cancer stages. In addition, we also performed correlation analysis between DNA sensors and their main signaling molecules to explore the possible mechanisms. The results showed that there were positive correlations between AIM2 and ASC/IL-18, DHX9 and MAVS, and TLR9 and MyD88 expression. In addition, the gene expression patterns of some DNA sensors were confirmed by Western-blot analysis. Conclusions: Our study revealed that the expression of multiple DNA sensors was deregulated in CRC and might be involved in tumor development. More importantly, the study identified that, among all these DNA sensors, AIM2, DAI, and DDX60 could be potentially critical for diagnosis, prognosis, and therapy of CRC and deserve further investigation.

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“…In total, 428 tissues obtained from primary BMSCC (n = 179) and TSCC (n = 249) between 1993 and 2006 were embedded in paraffin to construct a TMA, as described previously [19] Each patient tissue contained 1 core of adjacent normal tissue and 2 cores of tumor tissue in the TMA block. The blocks were cut in 4 µm paraffin sections.…”

Section: Tissue Specimens and Tissue Microarray (Tma) Constructionmentioning

confidence: 99%

Association of ATG4B and Phosphorylated ATG4B Proteins with Tumorigenesis and Prognosis in Oral Squamous Cell Carcinoma

Liu

Chen

Cheng

et al. 2019

Cancers

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Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide due to the limited availability of biomarkers and therapeutic targets. Autophagy related protease 4B (ATG4B) is an essential protease for the autophagy machinery, and ATG4B phosphorylation at Ser383/392 increases its proteolytic activity. ATG4B expression and activation are crucial for cancer cell proliferation and invasion. However, the clinical relevance of ATG4B and phospho-Ser383/392-ATG4B for OSCC remains unknown, particularly in buccal mucosal SCC (BMSCC) and tongue SCC (TSCC). With a tissue microarray comprising specimens from 498 OSCC patients, including 179 BMSCC and 249 TSCC patients, we found that the protein levels of ATG4B and phospho-Ser383/392-ATG4B were elevated in the tumor tissues of BMSCC and TSCC compared with those in adjacent normal tissues. High protein levels of ATG4B were significantly associated with worse disease-specific survival (DSS) in OSCC patients, particularly in patients with tumors at advanced stages. In contrast, phospho-Ser383/392-ATG4B expression was correlated with poor disease-free survival (DFS) in TSCC patients. Moreover, ATG4B protein expression was positively correlated with phospho-Ser383/392-ATG4B expression in both BMSCC and TSCC. However, high coexpression levels of ATG4B and phospho-Ser383/392-ATG4B were associated with poor DFS only in TSCC patients, whereas they had no significant association with DSS in BMSCC and TSCC patients. In addition, silencing ATG4B with an antisense oligonucleotide (ASO) or small interfering RNA (siRNA) diminished cell proliferation of TW2.6 and SAS oral cancer cells. Further, knockdown of ATG4B reduced cell migration and invasion of oral cancer cells. Taken together, these findings suggest that ATG4B might be a biomarker for diagnosis/prognosis of OSCC and a potential therapeutic target for OSCC patients.

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Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma

Cited by 31 publications

References 50 publications

Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

DNA sensors, crucial receptors to resist pathogens, are deregulated in colorectal cancer and associated with initiation and progression of the disease

Association of ATG4B and Phosphorylated ATG4B Proteins with Tumorigenesis and Prognosis in Oral Squamous Cell Carcinoma

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