RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival

Taniue, Kenzui; Tanu, Tanzina; Shimoura, Yuki; Mitsutomi, Shuhei; Han, Han; Kakisaka, Rika; Ono, Yoshio; Tamamura, Nobue; Takahashi, Kenji; Wada, Youichiro; Mizukami, Yusuke; Akimitsu, Nobuyoshi

doi:10.3390/ijms23010496

Cited by 12 publications

(8 citation statements)

References 70 publications

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“…On the other hand, the functions of genomic-proximal inter-chromosomal PPIs are relavent with RNA exosome and proteasome which mediate the degradation of RNA and protein (Makino et al, 2013). The degradation system was shown to play important roles in cancer studies (Manasanch and Orlowski, 2017; Taniue et al, 2022) and the two degradatioin systems may follow common principles (Makino et al, 2013). These results demonstrated the possible roles chromatin and corresponding protein complex structures may play for the establishment of cell identity, as the structural-related PPIs are in correspondence with the cell-specific biological processes.…”

Section: Resultsmentioning

confidence: 99%

Computational Enhanced Hi-C data reveals the function of structural geometry in genomic regulation

Xue

Wang

et al. 2022

Preprint

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High-throughput chromosome conformation capture (Hi-C) technique profiles the genomic structure in a genome-wide fashion. The reproducibility and consistency of Hi-C data are essential in characterizing dynamics of genomic structures. We developed a diffusion-based method, CTG (Hi-C To Geometry), to deal with the technical bias induced by insufficient sampling in sequencing and obtain reliable gemeotric information of the chromatin. CTG properly quantifies dubiously weak or even undetected interactions and produces a consistent and reproducible framework for the 3D genomic structure. CTG allows for a reliable genome-wide insight on the alteration of genomic structures under different cellular conditions and reveals correlations between genomic-proximal genes at both transcriptional and translational levels. Cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as that with the transcription correlation reveals the coordinated inter-molecular structural and regulatory information passage in the central dogma.

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Section: Resultsmentioning

confidence: 99%

Computational Enhanced Hi-C data reveals the function of structural geometry in genomic regulation

Xue

Wang

et al. 2022

Preprint

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“…TCGA Pan Cancer analysis revealed that exosome component 4 (EXOSC4) showed highlevel ampli cation in 9 cancer types, including Breast invasive carcinoma (BRCA). The alteration of EXOSC4 was associated with the OS and PFS pancreatic cancer patients [20]. Downregulation of EXOSC4 can inhibit cancer cell migration and invasion [21,22].…”

Section: Discussionmentioning

confidence: 96%

“…Downregulation of EXOSC4 can inhibit cancer cell migration and invasion [21,22]. Taniue et al also showed that EXOSC4 knockdown led to the reduction in the viability of pancreatic and colorectal tumor cells [20]. Awwad et al reported that the high IKZF3 expression in T-cells correlates with the OS in the patients of multiple myeloma stage III treated with immunomodulatory drugs [23].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel a chromatin regulator signature predicting overall survival for breast cancer

Liu

Zhou

et al. 2022

Preprint

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Background Breast cancer (BRCA) has the highest incidence among female malignancies. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. We aim to develop a chromatin regulators signature to predict the prognosis of BRCA patients. Methods The mRNA expression profiles and corresponding clinical data of BRCA patients were downloaded from TCGA databases, and then the differentially expressed CRs genes were screened. We also used the least absolute shrinkage and selection operator (LASSO) Cox regression model to construct a multigene signature with CRs genes of BRCA patients and evaluated the efficacy of the CRs prognostic signature with GEO validation cohort. Then, we explored the differences of tumor immune cell infiltration, tumor mutation burden (TMB), and patients’ response to chemotherapy between the different risk group. Results This CRs prognostic signature consisted of 8 chromatin regulators related genes, which was an independent prognostic factor of BRCA. The prognostic signature was further validated in GSE42568 cohort. According to the signature, patients with BRCA were divide into two risk groups. Functional annotation and the pathway analysis showed that the high-risk group had an enrichment of many tumor features, including cGMP-PKG signaling pathway, chromatin remodeling, DNA repair, thyroid cancer, cell cycle, homologous recombination, lysine degradation, pathways in cancer. Moreover, the immune cell types of tumor immune microenvironment and the TMB value of patients in the high-risk group was significantly different from those in low-risk group. ROC curves and nomogram indicated that the risk score had a good accuracy for predicting the survival of BRCA patients. Conclusions We identified a novel CRs prognostic signature which could precisely predict the prognosis of breast cancer patients. Our work elucidated that the CRs genes may serve as an indispensable player in complexity and diversity of tumor progression.

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“…Zhang et al reported that EXOSC2 might regulate tumor angiogenesis in esophageal cancer by accelerating the degradation of IFI27 mRNA 47 . Similarly, EXOSC4 has been shown to destabilize SESN2 mRNA, influencing the proliferation of pancreatic cancer cells 48 . However, the present study showed that the number of upregulated mRNAs was limited in EXOSC5-knockdown EC cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin β1 signalling axis

Huang,

Wang,

Wang

et al. 2024

Int. J. Biol. Sci.

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Endometrial carcinoma (EC) is a common type of uterine cancer in developed countries, originating from the uterine epithelium. The incidence rate of EC in Taiwan has doubled from 2005. Cancer stem cells (CSCs) are a subpopulation of cancer cells that have high tumorigenicity and play a crucial role in the malignant processes of cancer. Targeting molecules associated with CSCs is essential for effective cancer treatments. This study delves into the role of Exosome component 5 (EXOSC5) in EC. Data from The Cancer Genome Atlas suggests a correlation between high EXOSC5 mRNA expression and unfavorable EC prognosis. EXOSC5 knockdown diminished EC-CSC self-renewal and reduced expression of key cancer stemness proteins, including c-MYC and SOX2. Intriguingly, this knockdown significantly curtailed tumorigenicity and CSC frequency in EC tumor spheres. A mechanistic examination revealed a reduction in netrin4 (NTN4) levels in EXOSC5-depleted EC cells. Moreover, NTN4 treatment amplified EC cell CSC activity and, when secreted, NTN4 partnered with integrin β1, subsequently triggering the FAK/SRC axis to elevate c-MYC activity. A clear positive relation between EXOSC5 and NTN4 was evident in 93 EC tissues. In conclusion, EXOSC5 augments NTN4 expression, activating c-MYC via the integrin β1/FAK/SRC pathway, offering potential avenues for EC diagnosis and treatment.

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RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival

Cited by 12 publications

References 70 publications

Computational Enhanced Hi-C data reveals the function of structural geometry in genomic regulation

Computational Enhanced Hi-C data reveals the function of structural geometry in genomic regulation

Identification of novel a chromatin regulator signature predicting overall survival for breast cancer

EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin β1 signalling axis

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