Computational prediction and analysis of deleterious cancer associated missense mutations in DYNC1H1

Sucularli, Ceren; Arslantas, Melda

doi:10.1016/j.mcp.2017.04.004

Cited by 14 publications

(15 citation statements)

References 64 publications

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“…It is significantly upregulated in primary gallbladder carcinoma (PGC) and is a potential biomarker (20). Inactivating mutations of DYNC1H1 have been found to promote tumorigenesis in pancreatic cancer (21). The intermediate chain, DYNC1I1, has rarely been associated with tumors and its role in cancer remains controversial.…”

Section: Discussionmentioning

confidence: 99%

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression

Gong

Wen

et al. 2019

Front. Oncol.

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Gastric cancer is one of the top five malignant tumors worldwide. At present, the molecular mechanisms of gastric cancer progression are still not completely clear. Cytoplasmic dynein regulates intracellular transport and mitotic spindle localization, and its abnormal function is crucial for tumorigenesis, promotes tumor cell cycle progression, and tumor migration. DYNC1I1 is an important binding subunit of cytoplasmic dynein. However, studies on DYNC1I1 in tumors are currently limited. In the current study, we found that high DYNC1I1 expression in gastric cancer is associated with poor prognosis and is an independent prognostic factor. DYNC1I1 promoted the proliferation and migration of gastric cancer cells both in vitro and in vivo . DYNC1I1 also upregulated IL-6 expression by increasing NF-κB nuclear translocation. Collectively, these data revealed an important role for the DYNC1I1-driven IL-6/STAT pathway in gastric cancer proliferation and migration, suggesting that DYNC1I1 may be a potential therapeutic target for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression

Gong

Wen

et al. 2019

Front. Oncol.

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“…This suggests that SNRPB may play an essential role in cell division and DNA replication. Interestingly, a previous study showed that SNRPB interacted with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) (Prescott et al, 2014), a subunit of human cytoplasmic dynein complex that functions in intracellular transport of DNA damage proteins and mitotic spindle positioning in colorectal cancer (Sucularli and Arslantas, 2017). GESA data suggest SNRPB's participation in cell cycle regulation which is largely mediated by the tumor suppressor p53.…”

Section: Discussionmentioning

confidence: 99%

c‐Myc‐mediated SNRPB upregulation functions as an oncogene in hepatocellular carcinoma

Peng

et al. 2020

Cell Biology International

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Dysregulation of genes involved in alternative splicing contributes to hepatocarcinogenesis. SNRPB, a component of spliceosome, is implicated in human cancers, yet its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. Here, we show that SNRPB expression is increased in HCC tissues, compared with the nontumorous tissues, at both messenger RNA and protein levels in two independent cohorts. High expression of SNRPB is significantly associated with higher pathological grade, vascular invasion, serum alpha-fetoprotein level, tumor metastasis, and poor disease-free and overall survivals. Luciferase reporter and chromatin immunoprecipitation assays demonstrate that SNRPB upregulation in HCC is mediated by c-Myc. Positive correlation is found between SNRPB and c-Myc expression in clinical samples. In vitro studies show that ectopic expression of SNRPB promotes HCC cell proliferation and migration, whereas knockdown of SNRPB results in the opposite phenotypes. Collectively, our data suggest SNRPB function as an oncogene and serve as a potential prognostic factor in HCC.

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“…However, examining candidate missense mutations that may cause pathogenic alterations and identifying their relative effects on function is a time-consuming and labor-wasting process. Recently, computational prediction has been proposed as an efficient and economical strategy to screen for potential pathogenic missense mutations ( 36 ). By applying bioinformatics tools and databases in the present study, it was predicted that no identified missense mutations in APC or MUTYH were deleterious.…”

Section: Discussionmentioning

confidence: 99%

Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis

et al. 2018

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Familial adenomatous polyposis (FAP) is an autosomal dominant-inherited colorectal cancer. Recent advances in genetics have indicated that the majority of patients with FAP carry germline mutations of the adenomatous polyposis coli (APC) and mutY DNA glycosylase (MUTYH) genes. However, a large subset of families with a history of FAP have undetectable pathogenic alterations, termed APC/MUTYH mutation-negative FAP. To investigate the germline mutations in the APC and MUTYH genes in Chinese patients with FAP, 13 unrelated patients were enrolled. Through genetic sequencing, four known pathogenic alterations (Lys1061LysfsTer2, Glu1309AspfsTer4, Arg283Ter and Ser1196Ter) of APC and two novel disease-associated pathogenic mutations (Tyr152Ter and Ter522Gly) in MUTYH were identified in six individuals. For samples that did not present with pathogenic alterations, the functional effects of missense, synonymous and intronic mutations were analyzed using bioinformatics tools and databases. Bioinformatics prediction suggested that the synonymous mutation Tyr486Tyr in APC (APC∆486s) was likely a disease-causing polymorphism and may have induced the exon skipping of APC. A hybrid mini-gene assay was performed, which confirmed that the synonymous single nucleotide polymorphism APC∆486s induced major splicing defects with skipping of exon 12 in APC. The data of the present study suggested that the synonymous polymorphism APC∆486s was a potential pathogenic alteration that predisposed APC/MUTYH mutation-negative patients to FAP.

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Computational prediction and analysis of deleterious cancer associated missense mutations in DYNC1H1

Cited by 14 publications

References 64 publications

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression

c‐Myc‐mediated SNRPB upregulation functions as an oncogene in hepatocellular carcinoma

Synonymous mutation adenomatous polyposis coliΔ486s affects exon splicing and may predispose patients to adenomatous polyposis coli/mutY DNA glycosylase mutation‑negative familial adenomatous polyposis

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