EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells

Yoshino, Seiko; Matsui, Yusuke; Fukui, Yoshikazu; Seki, Masahide; Yamaguchi, Kiyoshi; Kanamori, Akane; Saitoh, Yurika; Shimamura, Teppei; Suzuki, Yutaka; Furukawa, Yoichi; Kaneko, Shuichi; Seiki, Motoharu; Murakami, Yoshinori; Inoue, Jun‐ichiro; Sakamoto, Takeharu

doi:10.1038/s41598-020-66455-2

Cited by 23 publications

(26 citation statements)

References 54 publications

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“…EXOSC8 was found to be promoting tumor and cancer cell growth in colorectal carcinoma [34]. Reduction in EXOSC9 was found to be associated with reduction of p-body formation in cancer cells [35]. From all these studies, we can infer that FRG1 along with EXOSC8 and EXOSC9 might play a major role in controlling RNA processing and its depletion can affect functional RNAs.…”

Section: Discussionmentioning

confidence: 87%

Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

Khan

Palo

Dixit

2021

Preprint

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FRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed FRG1 expression is associated with the overall survival (OS) in cancers the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 expression groups, but in breast, lung, and liver cancers the difference was not prominent. We hypothesized that the functionality of the genes correlated with FRG1 could be getting affected by FRG1 or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, and HIPPIE were used to deduce FRG1 associated pathways. In breast, lung, and liver cancer we found a distinct difference in the OS, between the low and high FRG1 expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups revealed a significant difference in the FRG1 expression and survival. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 expression on these genes by qRT-PCR, supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.

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Section: Discussionmentioning

confidence: 87%

Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

Khan

Palo

Dixit

2021

Preprint

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show abstract

“…EXOSC8 promoted tumor and cancer cell growth in colorectal carcinoma 46 . Reduction in EXOSC9 was associated with reducing of p-body formation in cancer cells 47 . From all these studies, we can infer that FRG1 along with EXOSC8 and EXOSC9 might play a major role in controlling RNA processing and, its depletion can affect functional RNAs.…”

Section: Discussionmentioning

confidence: 89%

Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

Khan

Palo

Dixit

2021

Sci Rep

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FRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed that FRG1 mRNA expression is associated with overall survival (OS) in certain cancers, but the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 mRNA expression groups, but the difference was not prominent in breast, lung, and liver cancers. We hypothesized that FRG1 expression level could affect the functionality of the correlated genes or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, HIPPIE, Gene Ontology, and DAVID (KEGG) were used to deduce FRG1 associated pathways. In breast, lung, and liver cancers, we found a distinct difference in the OS between the low and high FRG1 mRNA expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups showed a significant difference in the FRG1 mRNA expression level and OS. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 mRNA expression level on these genes by qRT-PCR supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators, which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.

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“…For some types of cancer patients, the increase of EXOSC9 activity is associated with a poor prognosis. Therefore, drugs targeting the RNA exosome complex or EXOSC9 activity may also be useful for these cancers (25). MiR-195-5p is a tumor-suppressor miRNA.…”

Section: Discussionmentioning

confidence: 99%

The predictive value of RNA binding proteins in colon adenocarcinoma

Luan¹,

Lu²,

Wang³

et al. 2021

J Gastrointest Oncol

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Background: RNA binding proteins (RBPs) play an important role in regulating post-transcriptional gene expression and have been reported to be closely associated with the occurrence and development of tumors. However, the effect of RBPs in colon cancer remains unclear.Methods: We downloaded clinical information and transcriptome data of colon adenocarcinoma (COAD) from the The Cancer Genome Atlas database (TCGA) database. After combining this data, we identified differentially expressed RBPs in normal and cancer tissues and subsequently performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Prognosis-related RBPs were identified via Cox regression analysis. The samples were randomly divided into two groups; an experimental group and a control group. A predictive model was constructed by dividing the experimental group into high-and low-risk subgroups based on the scores of the prognostic-related RBPs, and the prognosis of samples in these two subgroups was compared. Then, this model was applied to the control group. Finally, the model results were verified based on an online survival database and the Human Protein Atlas (HPA) database.Results: A total of 469 differentially expressed RBPs were identified in normal and cancer tissues. Ten prognosis-related RBPs were determined by Cox regression analysis. In the prognostic prediction model, the prognosis of high-risk patients in the experimental group was worse than that in the low-risk group, and the same result was obtained in the control group. In addition, the risk score in the Cox regression analysis showed that the model could be used as an independent prognostic factor (P<0.001). The results of the online survival analysis tool, HPA database, and the model were consistent.Conclusions: Some specific RBPs are significantly associated with the prognosis of patients with COAD, and this finding may provide important information for the future diagnosis and treatment of patients with COAD.

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EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells

Cited by 23 publications

References 54 publications

Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

The predictive value of RNA binding proteins in colon adenocarcinoma

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