Hepatocellular Carcinoma and Nuclear Paraspeckles: Induction in Chemoresistance and Prediction for Poor Survival

Kessler, Sonja M.; Hosseini, Kevan; Hussein, Usama Khamis; Kim, Kyoung Min; List, Markus; Schultheiss, Christina S.; Schulz, Marcel H.; Laggai, Stephan; Jang, Kyu Yun; Kiemer, Alexandra K.

doi:10.33594/000000055

Cited by 30 publications

(8 citation statements)

References 49 publications

(60 reference statements)

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“…Cawthorn et al reported that up-regulated HSP90B1 is related with distant metastasis [37]. Kessler et al reported that Paraspeckle Component 1 (PSPC1) is significantly related with poor prognosis in hepatocellular carcinoma [38]. The results in current study further supported the credibility of these findings above in previous researches.…”

Section: Discussionsupporting

confidence: 86%

Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application

Zhang

Huang

et al. 2019

J Transl Med

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BackgroundThe current study aimed to construct competing endogenous RNA (ceRNA) regulation network and develop two precision medicine predictive tools for colorectal cancer (CRC).MethodsDifferentially expressed (DE) analyses were performed between CRC tissues and normal tissues. A ceRNA regulation network was constructed based on DElncRNAs, DEmiRNAs, and DEmRNAs.ResultsFifteen mRNAs (ENDOU, MFN2, FASLG, SHOC2, VEGFA, ZFPM2, HOXC6, KLK10, DDIT4, LPGAT1, BEX4, DENND5B, PHF20L1, HSP90B1, and PSPC1) were identified as prognostic biomarkers for CRC by multivariate Cox regression. Then a Fifteen-mRNA signature was developed to predict overall survival for CRC patients. Concordance indexes were 0.817, 0.838, and 0.825 for 1-, 2- and 3-year overall survival. Patients with high risk scores have worse OS compared with patients with low risk scores.ConclusionThe current study provided deeper understanding of prognosis-related ceRNA regulatory network for CRC. Two precision medicine predictive tools named Smart Cancer Survival Predictive System and Gene Survival Analysis Screen System were constructed for CRC. These two precision medicine predictive tools can provide valuable precious individual mortality risk prediction before surgery and improve the individualized treatment decision-making.

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Section: Discussionsupporting

confidence: 86%

Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application

Zhang

Huang

et al. 2019

J Transl Med

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“…They stimulate migration of both types, i.e., cutaneous and uveal melanoma [66][67][68][69]. Their role in chemoresistance of cancer cells to therapeutics is discussed [70]. Therefore, their targeting by small inhibitors was recently proposed in the literature [71].…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

Novotný

Strnadová

Dvořánková

et al. 2020

Cancers

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Heterogeneous spheroids have recently acquired a prominent position in melanoma research because they incorporate microenvironmental cues relevant for melanoma. In this study, we focused on the analysis of microenvironmental factors introduced in melanoma heterogeneous spheroids by different dermal fibroblasts. We aimed to map the fibroblast diversity resulting from previously acquired damage caused by exposure to extrinsic and intrinsic stimuli. To construct heterogeneous melanoma spheroids, we used normal dermal fibroblasts from the sun-protected skin of a juvenile donor. We compared them to the fibroblasts from the sun-exposed photodamaged skin of an adult donor. Further, we analysed the spheroids by single-cell RNA sequencing. To validate transcriptional data, we also compared the immunohistochemical analysis of heterogeneous spheroids to melanoma biopsies. We have distinguished three functional clusters in primary human fibroblasts from melanoma spheroids. These clusters differed in the expression of (a) extracellular matrix-related genes, (b) pro-inflammatory factors, and (c) TGFβ signalling superfamily. We observed a broader deregulation of gene transcription in previously photodamaged cells. We have confirmed that pro-inflammatory cytokine IL-6 significantly enhances melanoma invasion to the extracellular matrix in our model. This supports the opinion that the aspects of ageing are essential for reliable melanoma 3D modelling in vitro.

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“…Chemoresistance is widespread in HCC and characterizes tumor progression [49]. Interestingly, TTP overexpression in PLC/PRF/5 cells decreased the expression of the long transcript variant of the long-non coding RNA NEAT1 , NEAT1_v2 , which has been reported to enhance chemoresistance in different cancer cell lines, including hepatoma cells [50,51]. NEAT1 is one of the least stable long non-coding RNAs [52], a presumed tumor promoter, and associated with chemoresistance [50,53].…”

Section: Discussionmentioning

confidence: 99%

The mRNA-binding Protein TTP/ZFP36 in Hepatocarcinogenesis and Hepatocellular Carcinoma

Kröhler

Kessler

Hosseini

et al. 2019

Cancers

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Hepatic lipid deposition and inflammation represent risk factors for hepatocellular carcinoma (HCC). The mRNA-binding protein tristetraprolin (TTP, gene name ZFP36) has been suggested as a tumor suppressor in several malignancies, but it increases insulin resistance. The aim of this study was to elucidate the role of TTP in hepatocarcinogenesis and HCC progression. Employing liver-specific TTP-knockout (lsTtp-KO) mice in the diethylnitrosamine (DEN) hepatocarcinogenesis model, we observed a significantly reduced tumor burden compared to wild-type animals. Upon short-term DEN treatment, modelling early inflammatory processes in hepatocarcinogenesis, lsTtp-KO mice exhibited a reduced monocyte/macrophage ratio as compared to wild-type mice. While short-term DEN strongly induced an abundance of saturated and poly-unsaturated hepatic fatty acids, lsTtp-KO mice did not show these changes. These findings suggested anti-carcinogenic actions of TTP deletion due to effects on inflammation and metabolism. Interestingly, though, investigating effects of TTP on different hallmarks of cancer suggested tumor-suppressing actions: TTP inhibited proliferation, attenuated migration, and slightly increased chemosensitivity. In line with a tumor-suppressing activity, we observed a reduced expression of several oncogenes in TTP-overexpressing cells. Accordingly, ZFP36 expression was downregulated in tumor tissues in three large human data sets. Taken together, this study suggests that hepatocytic TTP promotes hepatocarcinogenesis, while it shows tumor-suppressive actions during hepatic tumor progression.

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Hepatocellular Carcinoma and Nuclear Paraspeckles: Induction in Chemoresistance and Prediction for Poor Survival

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 30 publications

References 49 publications

Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application

Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application

Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids

The mRNA-binding Protein TTP/ZFP36 in Hepatocarcinogenesis and Hepatocellular Carcinoma

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