A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway

Background/Aims: The roles and related mechanisms of RNA binding protein FUS (fused in sarcoma/translocated in liposarcoma) are unclear in numerous cancers, including hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, transwell migration and invasion, tumor spheres formation and in vivo tumor formation assays were used to examine the effects of FUS on HCC progression in HuH7 and MHCC97 cells. Additionally, transcriptome analysis based on RNA-sequencing data, qRT-PCR, western blots, luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays were used to explore the LATS1/2 (large tumor suppressor kinases 1/2)-related mechanisms contributing to FUS functions. Finally, qRT-PCR and western blot analysis were used to detect the levels of FUS and LATS1/2 in HCC and adjacent normal tissues, and the correlation between them in HCC tissues. Results: Overexpression of FUS decreased cell viability, migration, invasion and stemness. Moreover, FUS interacted and stabilized LATS1/2 stability, and thus promoted LATS1/2 expression and activated Hippo pathway. Finally, FUS and LAST1/2 levels were positively correlated and significantly down-regulated in HCC tissues. Conclusion: We demonstrate that FUS/LATS1/2 axis inhibits HCC progression via activating Hippo pathway.

Download Full-text

The KH-type splicing regulatory protein (KSRP) regulates type III interferon expression post-transcriptionally

Biochemical Journal ◽

10.1042/bcj20180522 ◽

2019 ◽

Vol 476 (2) ◽

pp. 333-352 ◽

Cited By ~ 4

Author(s):

Lisa Schmidtke ◽

Katharina Schrick ◽

Sabrina Saurin ◽

Rudolf Käfer ◽

Fabian Gather ◽

...

Keyword(s):

Half Life ◽

Rna Binding ◽

Binding Protein ◽

Regulatory Protein ◽

Rna Binding Protein ◽

Luciferase Reporter ◽

Regulatory Function ◽

Type Iii ◽

Type Iii Ifn ◽

Mrna Half Life

Abstract Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell functions. Therefore, it is important to identify cellular mechanisms involved in the control of type III IFN expression. All IFN family members contain AU-rich elements (AREs) in the 3′-untranslated regions (3′-UTR) of their mRNAs that determine mRNA half-life and consequently the expressional level of these cytokines. mRNA stability is controlled by different proteins binding to these AREs leading to either stabilization or destabilization of the respective target mRNA. The KH-type splicing regulatory protein KSRP (also named KHSRP) is an important negative regulator of ARE-containing mRNAs. Here, we identify the interferon lambda 3 (IFNL3) mRNA as a new KSRP target by pull-down and immunoprecipitation experiments, as well as luciferase reporter gene assays. We characterize the KSRP-binding site in the IFNL3 3′-UTR and demonstrate that KSRP regulates the mRNA half-life of the IFNL3 transcript. In addition, we detect enhanced expression of IFNL3 mRNA in KSRP−/− mice, establishing a negative regulatory function of KSRP in type III IFN expression also in vivo. Besides KSRP the RNA-binding protein AUF1 (AU-rich element RNA-binding protein 1) also seems to be involved in the regulation of type III IFN mRNA expression.

Download Full-text

Identification of RNA binding protein interacting with circular RNA and hub candidate network for hepatocellular carcinoma

Aging ◽

10.18632/aging.203139 ◽

2021 ◽

Author(s):

Binglin Cheng ◽

Jingdong Tian ◽

Yuhan Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Circular Rna ◽

Candidate Network

Download Full-text

106 Nuclear Expression of RNA Binding Protein APOBEC-1 Complementation Factor (ACF) Regulates Liver Growth and Attenuates Tumorigenesis in Humans With Hepatocellular Carcinoma

Gastroenterology ◽

10.1016/s0016-5085(16)30217-7 ◽

2016 ◽

Vol 150 (4) ◽

pp. S27

Author(s):

Valerie Blanc ◽

Jesse D. Riordan ◽

Eddie Park ◽

Susan Kennedy ◽

Blair Madison ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Liver Growth ◽

Nuclear Expression

Download Full-text

Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers12113397 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3397

Author(s):

Leyre Silva ◽

Josune Egea ◽

Lorea Villanueva ◽

Marta Ruiz ◽

Diana Llopiz ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cell ◽

Rna Binding ◽

Checkpoint Inhibitors ◽

Binding Protein ◽

Rna Binding Protein ◽

T Cell Responses ◽

Tumor Infiltrating Lymphocytes ◽

Cell Responses ◽

Tlr4 Ligand

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered.

Download Full-text

The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production

EBioMedicine ◽

10.1016/j.ebiom.2019.06.030 ◽

2019 ◽

Vol 45 ◽

pp. 155-167 ◽

Cited By ~ 30

Author(s):

Wei Dong ◽

Zhi-hui Dai ◽

Fu-chen Liu ◽

Xing-gang Guo ◽

Chun-mei Ge ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Circular Rna

Download Full-text

Chimeric RNA binding protein based killing switch targeting hepatocellular carcinoma cells

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2021.08.012 ◽

2021 ◽

Author(s):

Jiong Yang ◽

Shigang Ding

Keyword(s):

Hepatocellular Carcinoma ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Chimeric Rna

Download Full-text

RNA-binding protein Dnd1 inhibits epithelial–mesenchymal transition and cancer stem cell-related traits on hepatocellular carcinoma cells

Biotechnology Letters ◽

10.1007/s10529-017-2375-5 ◽

2017 ◽

Vol 39 (9) ◽

pp. 1359-1367 ◽

Cited By ~ 4

Author(s):

Weiling Xu ◽

Fangchao Gong ◽

Ting Zhang ◽

Baorong Chi ◽

Jingyu Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cell ◽

Cancer Stem Cell ◽

Rna Binding ◽

Epithelial Mesenchymal Transition ◽

Binding Protein ◽

Rna Binding Protein ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Mesenchymal Transition

Download Full-text

Long noncoding RNA HOTAIR mediates the estrogen-induced metastasis of endometrial cancer cells via the miR-646/NPM1 axis

AJP Cell Physiology ◽

10.1152/ajpcell.00222.2017 ◽

2018 ◽

Vol 314 (6) ◽

pp. C690-C701 ◽

Cited By ~ 24

Author(s):

Yun-xiao Zhou ◽

Chuan Wang ◽

Li-wei Mao ◽

Yan-li Wang ◽

Li-qun Xia ◽

...

Keyword(s):

Noncoding Rna ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Protein ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Qrt Pcr ◽

Reporter Assays ◽

Ec Cells

LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been confirmed to be involved in the tumorigenic progression of endometrial carcinoma (EC). However, the molecular mechanisms of HOTAIR in EC are not fully elucidated. The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT-PCR. The effect of miR-646 on EC cells was assessed by the cell viability, migration, and invasion using CCK-8 assays and transwell assays. RNA-binding protein immunoprecipitation assays and RNA pull-down assays were performed to explore the interaction between HOTAIR and miR-646. The regulation of miR-646 on nucleophosmin 1 (NPM1) was tested using luciferase reporter assays. MiR-646 expression was significantly decreased both in human EC tissues ( n = 23) and cell lines (Ishikawa and HEC-1-A) compared with the control. Moreover, miR-646 expression was negatively related to HOTAIR in human EC tissues ( n = 23). Our results also showed that miR-646 overexpression considerably attenuated the E2-promoted viability, migration, and invasion of Ishikawa and HEC-1-A cells in vitro. In addition, HOTAIR was confirmed to regulate the viability, migration, and invasion of EC cells through negative regulating miR-646. More importantly, we also demonstrated that NPM1 was the target of miR-646, and HOTAIR promoted NPM1 expression through interacting with miR-646 in EC cells. Taken together, our findings presented that HOTAIR could regulate NPM1 via interacting with miR-646, thereby governing the viability, migration, and invasion of EC cells.

Download Full-text