Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression

Peng, Wen; Zhang, Chuan; Peng, Jianing; Huang, Yuesheng; Peng, Cong; Tan, Yuqian; Ji, Dongjian; Zhang, Yue; Zhang, Dongsheng; Tang, Junwei; Feng, Yifei; Sun, Yueming

doi:10.1016/j.canlet.2020.08.036

Cited by 30 publications

(23 citation statements)

References 42 publications

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“…However, recently studies revealed that RNA binding protein plays a crucial role in LncRNA regulating network. Peng et al revealed that Lnc-FAM84B-4 interacts with protein hnRNPK to restrain MAPK pathway, leading to CRC progression 21 . Klingenberg et al indicated that CASC9/hnRNPL serves as a lncRNA/protein complex associated with clinically relevant viability and affects AKT signaling in HCC 22 .…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

Tan

Chen

et al. 2021

Cell Death Dis

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The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa). SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the RNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism. We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial–mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.

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Section: Discussionmentioning

confidence: 99%

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

Tan

Chen

et al. 2021

Cell Death Dis

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“…Plenty of studies have demonstrated that various posttranslational modi cations of hnRNPK, including phosphorylation, ubiquitination, methylation, and SUMOylation, play critical roles in hnRNPK function coactivation (15). Although several circRNAs have been reported to interact with hnRNPK, the circRNA that regulates the posttranslational modi cation of hnRNPK has not been reported yet (24,25,42). On top of that, the role of circRNA in the SUMOylation of protein has not been researched.…”

Section: Discussionmentioning

confidence: 99%

“…HnRNPK was reported to work as a DNA and RNA binding protein and regulate a large number of biological processes and cancer pathogenesis (14). Additionally, previous studies had explored that hnRNPK could in uence CRC progression by interacting with noncoding RNA (24,25). Then, hnRNPK silencing cells were constructed (Fig.…”

Section: Circ-galnt16 Suppresses the Progression Of Crc By Speci Cally Binding To The Kh3 Domain Of Hnrnpkmentioning

confidence: 99%

Circ-GALNT16 Restrains Colorectal Cancer Progression by Enhancing the SUMOylation of hnRNPK

Peng

Tan

Yang

et al. 2021

Preprint

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BackgroundEmerging studies have investigated circRNAs as significant regulation factors in multiple cancer progression. Nevertheless, the biological functions and underlying mechanisms of circRNAs in colorectal cancer progression remain unclear.MethodsA novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of phenotype experiments in vitro and vivo were performed to investigate the role of circ-GALNT16 in CRC. FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were constructed to explore the molecular mechanisms of circ-GALNT16 in colorectal cancer.ResultsCirc-GALNT16 was downregulated in colorectal cancer and negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastasis ability of colorectal cancer in vitro and vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which resulted in the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. Furthermore, RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex.ConclusionsCirc-GALNT16 suppressed CRC progression via inhibiting Serpine1 expression through adjusting the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might work as a biomarker and therapeutic target for CRC.

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“…For target protein mutation and segmentation, ALDOA was mutated on ve sites separately: E35D, K42N/R43A, K149A, K294A (Boshang, China) according to the former studies [19,20]. Considering the interaction between ALDOA and ARST according to the prognosis results on catRAPID website, ALDOA was also designed to be segmented into two parts (Boshang, China).…”

Section: Peptide Mutation and Segmentation Assaymentioning

confidence: 99%

A Novel lncRNA ARST Represses Glioma Progression by Inhibiting ALDOA-mediated Actin Cytoskeleton Integrity

Sun

et al. 2020

Preprint

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Background: Glioma is one of the most aggressive malignant brain tumors that is characterized with highly infiltrative growth and poor prognosis. ARST is a novel lncRNA which expression is significantly decreased in the patients with glioblastoma multiforme. However, the exact mechanisms of ARST in gliomagenesis are largely unknown. Methods: The expressions of ARST in the glioma samples and cell lines were analyzed by qRT-PCR. FISH was utilized to detect the distribution of ARST in the glioma cells. CCK-8, EdU and flow cytometry were used to examine cellular viability, proliferation and apoptosis. Transwell and wound-healing assays were performed to determine the migratory and invasive abilities of the cells. Intracranial tumorigenesis models were established to explore the roles of ARST in vivo. RNA pulldown assay was used to examine proteins that bound to ARST. The activities of key enzymes in the glycolysis and production of lactate acid were measured by colorimetry. In addition, RIP, Co-IP, western blot, immunofluorescence were used to investigate the interaction and regulation between ARST, F-actin, ALDOA and cofilin.Results: In this study, we reported that ARST was downregulated in the gliomas. Overexpression of ARST in the glioma cells significantly suppressed various cellular vital abilities such as cell growth, proliferation, migration and invasion. The tumorigenic capacity of these cells in vivo was reduced as well. We further demonstrated that the tumor suppressive effects of ARST could be mediated by a direct binding to a glycolytic enzyme aldolase A (ALDOA), which together with cofilin, keeps the polymerization and depolymerization of actin filaments in an orderly dynamic equilibrium. Upregulation of ARST interrupted the interaction of ALDOA and actin cytoskeleton, which led to a rapid cofilin-dependent loss of F-actin stress fibers. Conclusions: Taken together, it is concluded that ARST performs its function via a non-metabolic pathway associated with ALDOA, which otherwise modifies the morphology and invasive properties of the glioma cells. This has added new perspective to its role in tumorigenesis, thus providing potential target for glioma diagnosis, therapy, and prognosis.

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Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression

Cited by 30 publications

References 42 publications

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

Circ-GALNT16 Restrains Colorectal Cancer Progression by Enhancing the SUMOylation of hnRNPK

A Novel lncRNA ARST Represses Glioma Progression by Inhibiting ALDOA-mediated Actin Cytoskeleton Integrity

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Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression

Cited by 30 publications

References 42 publications

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer

Circ-GALNT16 Restrains Colorectal Cancer Progression by Enhancing the SUMOylation of hnRNPK

A Novel lncRNA&nbsp;ARST&nbsp;Represses Glioma Progression by Inhibiting ALDOA-mediated Actin Cytoskeleton Integrity

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A Novel lncRNA ARST Represses Glioma Progression by Inhibiting ALDOA-mediated Actin Cytoskeleton Integrity