Association between aberrant dynein cytoplasmic�1 light intermediate chain�1 expression levels, mucins and chemosensitivity in colorectal cancer

Chang, Chao-Sung; Chao, Kuo-Ching; Huang, Chun-Ta; Hung, Chi‐Ren; Wang, Yen-Chieh

doi:10.3892/mmr.2020.11086

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…Varying levels of gene expression in stool specimens were reflected at the respective protein and mRNA levels in the tissues using immunohistochemistry and the CRC cDNA array, respectively. As previously reported by the authors, DYNC1LI1 was expressed at a significantly higher level in cDNA samples from patients with distant metastasis than in cDNA samples from non-metastatic patients and in normal colonic tissues (77). In addition, increased (UBE2N and IMPDH1) and decreased (HRASLS2) cDNA levels were observed to be statistically significant for CRC tissues of all stages (P=0.020 for UBE2N, P=0.032 for IMPDH1 and P<0.001 for HRASLS2) compared with those detected in eight cDNA samples of non-CRC tissues in the HCRT104 cDNA array (Table SIV).…”

Section: Discussionsupporting

confidence: 82%

Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens

et al. 2023

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Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide. The poor specificity and sensitivity of the fecal occult blood test has prompted the development of CRC-related genetic markers for CRC screening and treatment. Gene expression profiles in stool specimens are effective, sensitive and clinically applicable. Herein, a novel advantage of using cells shed from the colon is presented for cost-effective CRC screening. Molecular panels were generated through a series of leave-one-out cross-validation and discriminant analyses. A logistic regression model following reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry was used to validate a specific panel for CRC prediction. The panel, consisting of ubiquitin-conjugating enzyme E2 N (UBE2N), inosine monophosphate dehydrogenase 1 (IMPDH1), dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) and phospholipase A and acyltransferase 2 (HRASLS2), accurately recognized patients with CRC and could thus be further investigated as a potential prognostic and predictive biomarker for CRC. UBE2N, IMPDH1 and DYNC1LI1 expression levels were upregulated and HRASLS2 expression was downregulated in CRC tissues. The predictive power of the panel was 96.6% [95% confidence interval (CI), 88.1-99.6%] sensitivity and 89.7% (95% CI, 72.6-97.8%) specificity at a predicted cut-off value at 0.540, suggesting that this four-gene panel testing of stool specimens can faithfully mirror the state of the colon. On the whole, the present study demonstrates that screening for CRC or cancer detection in stool specimens collected non-invasively does not require the inclusion of an excessive number of genes, and colonic defects can be identified via the detection of an aberrant protein in the mucosa or submucosa.

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Section: Discussionsupporting

confidence: 82%

Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens

et al. 2023

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“…DYNC1LI1 encodes part of a protein complex (dynein cytoplasmic 1 light intermediate chain 1) responsible for converting energy from ATP hydrolysis into mitotic spindle function, with proposed important roles in cell division and migration [59,68]. Although not previously reported in DIPG to our knowledge, altered expression of DYNC1LI1 has been described in other malignancies (colorectal cancer and breast cancer in adults), with potential impact on therapy sensitivity [5,12,34]. Additionally, the presence of alterations in SRGAP3 and OR7E24 genes, which have also not previously been described in DIPG, were identified in a subset of patients and associated with overall survival (worse and better, respectively).…”

Section: Discussionmentioning

confidence: 95%

A pilot radiogenomic study of DIPG reveals distinct subgroups with unique clinical trajectories and therapeutic targets

Zhu

Lazow

Schafer

et al. 2021

acta neuropathol commun

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An adequate understanding of the relationships between radiographic and genomic features in diffuse intrinsic pontine glioma (DIPG) is essential, especially in the absence of universal biopsy, to further characterize the molecular heterogeneity of this disease and determine which patients are most likely to respond to biologically-driven therapies. Here, a radiogenomics analytic approach was applied to a cohort of 28 patients with DIPG. Tumor size and imaging characteristics from all available serial MRIs were evaluated by a neuro-radiologist, and patients were divided into three radiographic response groups (partial response [PR], stable disease [SD], progressive disease [PD]) based on MRI within 2 months of radiotherapy (RT) completion. Whole genome and RNA sequencing were performed on autopsy tumor specimens. We report several key, therapeutically-relevant findings: (1) Certain radiologic features on first and subsequent post-RT MRIs are associated with worse overall survival, including PD following irradiation as well as present, new, and/or increasing peripheral ring enhancement, necrosis, and diffusion restriction. (2) Upregulation of EMT-related genes and distant tumor spread at autopsy are observed in a subset of DIPG patients who exhibit poorer radiographic response to irradiation and/or higher likelihood of harboring H3F3A mutations, suggesting possible benefit of upfront craniospinal irradiation. (3) Additional genetic aberrations were identified, including DYNC1LI1 mutations in a subgroup of patients with PR on post-RT MRI; further investigation into potential roles in DIPG tumorigenesis and/or treatment sensitivity is necessary. (4) Whereas most DIPG tumors have an immunologically “cold” microenvironment, there appears to be a subset which harbor a more inflammatory genomic profile and/or higher mutational burden, with a trend toward improved overall survival and more favorable radiographic response to irradiation, in whom immunotherapy should be considered. This study has begun elucidating relationships between post-RT radiographic response with DIPG molecular profiles, revealing radiogenomically distinct subgroups with unique clinical trajectories and therapeutic targets.

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“…The several subunits that make up dynein include the heavy, intermediate, light intermediate and light chains. Dynein cell light intermediate chain 1 (DYNC1LI1) influences the sensitivity of colorectal cancer to radiation and chemotherapy and is linked to pancreatic ductal adenocarcinoma, hepatocellular carcinoma and prostate cancer 33 . Prostate cancer development has also been shown to be regulated by axonemal dynein heavy chain 8 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Dynein cell light intermediate chain 1 (DYNC1LI1) influences the sensitivity of colorectal cancer to radiation and chemotherapy and is linked to pancreatic ductal adenocarcinoma, hepatocellular carcinoma and prostate cancer. 33 Prostate cancer development has also been shown to be regulated by axonemal dynein heavy chain 8. 34 In conclusion, dynein may influence cell division, which might contribute to the development of tumours.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis indicated that NDE1 is a potential biomarker for pan‐cancer and promotes bladder cancer progression

Wang,

Ning,

Chen

et al. 2024

Cancer Medicine

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BackgroundThe nuclear distribution E homologue 1 (NDE1) is a crucial dynein binding partner. The NDE1 protein has the potential to disrupt the normal functioning of centrosomes, leading to a compromised ability to generate spindles and ensure precise separation of chromosomes during cell division. The potential consequences of this phenomenon include genomic instability, malignant transformation and the proliferation of neoplastic growths. However, studies examining the connection between NDE1 and cancer is still very rare.MethodsThe expression level, prognostic impact, gene change, DNA methylation, protein interaction, mRNA m6A modification, ceRNA network, associated gene and function enrichment, and immune‐related effects of NDE1 in pan‐cancer were examined using a range of online analytic tools and the R software package. The CCK‐8 test, transwell assay, scratch assay and colony formation assay were used to confirm the effects of NDE1 on the proliferation, invasion and metastasis of bladder cancer cells.ResultsNumerous tumour types have elevated NDE1, which is linked to a bad prognosis. NDE1 is an excellent diagnostic tool for many different types of cancer. Numerous malignancies have been linked to genetic changes in NDE1. NDE1 was connected to TMB, MSI, several immunological checkpoint genes and immune cell infiltration. NDE1 is linked to a number of immunological subtypes. NDE1 could affect how well immunotherapy works to treat different types of cancer. NDE1 was mostly associated with cell cycle, chromosomal segregation, DNA replication and mitotic segregation, according to GO and KEGG analyses. NDE1 physically binds to PAFAH1B1 and DCTN1, respectively. The proliferation, invasion and metastasis of bladder cancer cells may be prevented by NDE1 knockdown. Furthermore, knockdown of NDE1 promoted the apoptosis of bladder cancer cells.ConclusionHigh expression of NDE1 is present in a variety of tumours, which is linked to a bad prognosis for cancer. Knockdown of NDE1 inhibited the proliferation, invasion and metastasis of bladder cancer cells, and promoted the apoptosis. For a number of malignancies, NDE1 may be a biomarker for immunotherapy and prognosis.

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Association between aberrant dynein cytoplasmic�1 light intermediate chain�1 expression levels, mucins and chemosensitivity in colorectal cancer

Cited by 7 publications

References 42 publications

Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens

Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens

A pilot radiogenomic study of DIPG reveals distinct subgroups with unique clinical trajectories and therapeutic targets

Comprehensive analysis indicated that NDE1 is a potential biomarker for pan‐cancer and promotes bladder cancer progression

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