Oncogene RNA helicase DDX6 promotes the process of c‐Myc expression in gastric cancer cells

Taniguchi, Kohei; Iwatsuki, Ayako; Sugito, Nobuhiko; Shinohara, Haruka; Kuranaga, Yuki; Oshikawa, Yuki; Tajirika, Toshihiro; Futamura, Manabu; Yoshida, Kazuhiro; Uchiyama, Kazuhisa; Akao, Yukihiro

doi:10.1002/mc.22781

Cited by 35 publications

(27 citation statements)

References 32 publications

(85 reference statements)

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“…DDX46 is a member of the DDX RNA helicase family with ATP-dependent RNA helicase, that is located on chromosome 5q31.1 and plays a critical role in transcript splicing and ribosome assembly ( 20 ). Previous studies ( 21 – 23 ) in zebrafish have shown that DDX46 is required in the multilineage differentiation of hematopoietic stem cells and in the development of digestive organs and the brain.…”

Section: Discussionmentioning

confidence: 99%

DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma

et al. 2020

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dead-Box Helicase 46 (ddX46) is an aTP-dependent rna helicase that plays a central role in transcription splicing and ribosome assembly. However, the role of ddX46 in cutaneous squamous cell carcinoma (cScc) remains to be elucidated. The aim of the present study was to investigate the role of ddX46 in cScc by assessing ddX46 expression levels in cScc tissues and cell lines. The effect of ddX46 silencing on cScc cell proliferation, apoptosis and autophagy were also analyzed. it was demonstrated that ddX46 was significantly overexpressed in cScc tissues and cells (P<0.05). Furthermore, it was found that ddX46 silencing could dramatically inhibit cell proliferation (P<0.05). Moreover, cell apoptosis and autophagy were activated in ddX46 silencing groups (P<0.05). Therefore, the present results suggested that ddX46 was overexpressed in cScc and that ddX46 silencing can inhibit cell proliferation by inducing apoptosis and activating autophagy. Thus, ddX46 may serve as a novel potential therapeutic target for cScc.

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Section: Discussionmentioning

confidence: 99%

DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma

et al. 2020

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“…DDX6 binds to the 5′UTR of its target mRNA and recruits ribosomes, resulting in the initiation of translation (Supplementary Figure S5). In our previous studies, we detected the overexpression of DDX6 in most of the tumor samples and cell lines examined, and found that DDX6 positively regulates c-Myc expression at the translational step in various cancers [22,23,24]. Furthermore, DDX6 also positively regulates HER2 expression at the translation step in GC cells [16].…”

Section: Discussionmentioning

confidence: 99%

Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase

Tokumaru

Tajirika

Sugito

et al. 2019

IJMS

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Gastric cancer (GC) is one of the most common cancers worldwide. In the clinical setting, the identification of HER2 overexpression in GC was a significant finding, as trastuzumab, an anti-HER2 drug, provides a survival advantage to HER2-positive GC patients. In HER2-postive GC, the dysregulation of PI3K/AKT and MAPK/ERK signaling pathways has been reported, and inhibition of these pathways is an important therapeutic strategy. MiR-143 is known to act as a tumor suppressor in several cancers, such as bladder cancer, breast cancer, colorectal cancer, and gastric cancer. In the current study, we developed a novel chemically-modified miR-143 and explored the functions of this synthetic miR-143 (syn-miR-143) in HER2-positive gastric cancer. The expression level of miR-143 was down-regulated in GC cell lines, including HER2-positive GC cell lines, MKN7, and KATO-III. The ectopic expression of miR-143 in those cell lines suppressed cell growth through systemic silencing of KRAS and its effector signaling molecules, AKT and ERK. Furthermore, syn-miR-143 indirectly down-regulated the expression of HER2, an upstream molecule of KRAS, through silencing DEAD/H-box RNA helicase 6 (DDX6), RNA helicase, which enhanced HER2 protein expression at the translational step in HER2-positive GC cells. These findings suggested that syn-miR-143 acted as a tumor suppressor through the impairment of KRAS networks including the DDX6.

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“…Previously, we reported that oncogenic RNA helicase DDX6 was highly overexpressed in most of the malignant cell lines and clinical colorectal tumors that we had tested [ 7 , 8 ]. We also showed that DDX6 expression is linked to the regulation of translation of c-myc mRNA through the internal ribosome entry site (IRES) [ 9 ]. In addition, the DDX6 protein is most likely to interact with the 5-cap-structure binding protein eIF4E [ 6 , 10 ], which is a rate-limiting factor serving as a translation regulator for initiating translation.…”

Section: Discussionmentioning

confidence: 99%

DEAD-Box Protein RNA-Helicase DDX6 Regulates the Expression of HER2 and FGFR2 at the Post-Transcriptional Step in Gastric Cancer Cells

Tajirika

Tokumaru

Taniguchi

et al. 2018

IJMS

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The human DEAD/H-box RNA helicase DDX6 (RCK/p54) is a protein encoded by the fusion gene from the t(11;14)(q23;q32) chromosomal translocation observed in human B-cell lymphoma cell line RC-K8. DDX6 has a variety of functions such as translation initiation, pre-mRNA splicing, and ribosome assembly. However, details of the regulatory mechanism governing DDX6 and the functions of DDX6 are largely unknown. Previously, we reported that DDX6 is overexpressed in most malignant cell lines and clinical colorectal tumor samples and that DDX6 positively contributes to the pathogenesis of various cancers. In the current study, we aimed at revealing the function of DDX6 in HER2 and FGFR2 related human gastric cancer (GC) by using clinical samples and GC cell lines. DDX6 protein was overexpressed in about 60% of the clinical samples; HER2, in 35%; and FGFR2, in 30%, (n = 20). Interestingly, the DDX6 protein was overexpressed in all HER2-positive samples (n = 7), and in 83% (5 of 6) of the FGFR2-positive samples, which could reflect the contribution of DDX6 to the expression of HER2 and FGFR2. In the GC cell line MKN7, which has HER2 amplification, the knockdown of DDX6 by siR-DDX6 led to the decreased expression of the HER2 protein. On the other hand, the knockdown of HER2 did not influence the DDX6 expression. Similar results were also obtained for the KATO-III and HSC39 cell lines having amplified FGFR2 expression. The increased expression of DDX6 induced a significantly increased expression of the HER2 protein without increasing the mRNA expression. The results of an RNP Immunoprecipitation (RIP)-assay using GC cells indicated that the DDX6 protein acted as an RNA-binding protein for HER2 and FGFR2 mRNAs and positively regulated their post-transcriptional processes. These findings demonstrated that DDX6 was an upstream molecule that positively regulated the expression of HER2 and FGFR2 at the post-transcriptional step in GC cells.

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Oncogene RNA helicase DDX6 promotes the process of c‐Myc expression in gastric cancer cells

Cited by 35 publications

References 32 publications

DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma

DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma

Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase

DEAD-Box Protein RNA-Helicase DDX6 Regulates the Expression of HER2 and FGFR2 at the Post-Transcriptional Step in Gastric Cancer Cells

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