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Last update 08 May 2025

KHSRP

Last update 08 May 2025

Basic Info

Synonyms

Far upstream element-binding protein 2, FBP2, FUBP2

+ [6]

Introduction

Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.

Drugs associated with KHSRP

DKC1125

Target

KHSRP

Mechanism

KHSRP inhibitors

Active Org.

Chonnam National University

Originator Org.

Chonnam National University

Active Indication

Colorectal Liver Metastases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KHSRP

100 Translational Medicine associated with KHSRP

0 Patents (Medical) associated with KHSRP

279

Literatures (Medical) associated with KHSRP

01 Dec 2025·Inflammation Research

The RNA-binding protein KSRP reduces asthma-like characteristics in a murine model

Article

Author: Tubbe, Ingrid ; Lakus, Jelena ; Bros, Matthias ; Palzer, Kim-Alicia ; Bolduan, Vanessa ; Montermann, Evelyn ; Clausen, Björn E ; Pautz, Andrea

AbstractBackground and objectiveAsthma is a chronic inflammatory disease characterized by dysregulated cytokine expression. The RNA-binding protein KSRP reduces the expression of several pro-inflammatory mediators. Therefore, we investigated whether KSRP modulates Th2-associated immune responses in vivo in an ovalbumin-induced (OVA) allergic asthma model in C57BL/6 KSRP-deficient mice (KSRP−/−).MethodsAsthma severity in OVA-immunized wild type or KSRP−/− mice was determined by airway hyperresponsiveness (AHR), structural changes of lung tissue, and OVA-specific antibody production. Cytokine expression in bronchoalveolar lavage fluid (BALF) was measured by Cytometric Bead Array (CBA) analysis. Cellular signaling pathways involved in KSRP-mediated effects in asthma pathogenesis were analyzed in vitro in cell culture models using specific inhibitors.ResultsKSRP deficiency exacerbates OVA-induced allergic asthma compared to wild type mice, as indicated by increased AHR, more severe lung damage, goblet cell hyperplasia and increased OVA-specific antibody production. CBA analyses confirmed, that KSRP deficiency enhances IL-4, IL-5 and IL-13 production in BALF. The effect of KSRP on Th2-associated cytokine expression appears to be mediated by modulation of the STAT6 and NFAT signaling pathway rather than by inhibiting the stability of cytokine-encoding mRNA species.ConclusionOur data demonstrate that KSRP dampens Th2 immune cell activity and therefore seems to be important for the pathogenesis of Th2-mediated diseases.

11 Apr 2025·Science Advances

Androgen receptor–regulated lncRNA PRCAT71 promotes AR signaling through the interaction with KHSRP in prostate cancer

Article

Author: Yang, Yongyong ; Dong, Xuesen ; Lu, Jiawen ; Wan, Yu ; Guo, Qingxiang ; Yang, Rendong ; Yum, Chaehyun ; Schaeffer, Edward M. ; Fry, Joshua ; Wang, Ting-You ; Ji, Zhe ; Li, Qianru ; Liu, Qi ; Wang, Rui ; Ren, Yanan ; Lotan, Tamara L. ; Cao, Qi ; Weiner, Adam B.

Mounting evidence indicates that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in prostate cancer (PCa) are still largely unknown. In this study, we found an lncRNA, PCa-associated transcript 71 (PRCAT71), highly expressed in metastatic and primary PCa compared to benign prostate tissues. Silencing PRCAT71 inhibited cancerous properties of PCa cells and androgen receptor (AR) signaling. Mechanistically, PRCAT71 acts as a scaffold to recruit K homology (KH)–type splicing regulatory protein (KHSRP) to AR messenger RNA (mRNA) and stabilize AR mRNA, leading to activated AR signaling. KHSRP plays a critical role in PCa progression. PRCAT71 is transcriptionally regulated by AR-driven enhancers, forming a positive regulatory loop between AR and PRCAT71 in PCa. Our study demonstrates a coordinated regulation of AR mRNA by lncRNA PRCAT71 and RNA binding protein KHSRP and provides insight that the PRCAT71-KHSRP-AR axis is a promising therapeutic target for treating PCa.

01 Apr 2025·Journal of Cachexia, Sarcopenia and Muscle

Balancing LncRNA H19 and miR‐675 Bioconversion as a Key Regulator of Embryonic Myogenesis Under Maternal Obesity

Article

Author: Chen, Yanting ; Murdoch, Gordon K. ; Gao, Yao ; Liu, Xiangdong ; Zhu, Mei‐Jun ; Hossain, Md Nazmul ; Zhao, Liang ; Deavila, Jeanene Marie ; Du, Min

ABSTRACTBackgroundMaternal obesity (MO) impairs fetal skeletal muscle development, but the underlying mechanisms remain poorly defined. The regulatory roles of lncRNA H19 and its first exon derived microRNA675 (miR675) in prenatal muscle development remain to be examined. H19/Igf2 are in the same imprinting cluster with H19 expressed from the maternal allele while Igf2 expresses paternally. H19 contains a G‐rich loop, and KH‐type splicing regulatory protein (KHSRP) mediates the biogenesis of pre‐miRNAs containing G‐rich loops, which depends on its phosphorylation by AKT, a key mediator of IGF2 signalling. This study aims to depict the elusive function of these regulators that are affected by MO during embryonic myogenesis.MethodsSingle‐cell transcriptomic sequencing and GeoMx spatial RNA sequencing were performed to identify the differentially expressed genes between embryos from MO and control (CT) mice. Both E11.5 and E13.5 embryos were collected and analysed to validate the sequencing data. The roles of H19 and miR657 in myogenesis were further analysed in P19 embryonic cells via CRISPR/dCas9‐mediated H19 activation and inhibition. The epigenetic changes of H19 were analysed by methylated DNA immunoprecipitation, and allele‐targeted analysis of H19 was performed by crossing C57BL/6J and CAST/EiJ mice.ResultsTranscriptomic analysis showed that MO embryos contained less differentiated myocytes (1.34%) than CT embryos (2.86%). Myogenesis‐related GO biological processes were down‐regulated in the MO embryonic myotome region. MO embryos showed lower expression of myogenic transcription factors such as Myf5, Myod1, Myog, Mef2c and Myh3 (p < 0.05). MO altered epigenetic modifications of the H19 genomic cluster, showing a decreased methylation level in H19 imprinting control region (p < 0.05) and a diallelic expression pattern of H19, which elevated its expression in MO embryos. Overexpression of H19 inhibited myogenesis in P19 cells, but miR675 promoted myogenesis, suggesting the critical regulatory roles of bioconversion of H19 to miR675. A KHSRP mediates the biogenesis of miR675, a process that relies on its phosphorylation by IGF2/AKT signalling. Knocking‐down of KHSRP and inhibition of AKT abolished miR675 biogenesis. MO suppressed IGF2/AKT signalling and blocked KHSRP‐dependent miR675 biogenesis in embryos.ConclusionsWe found differential effects of H19 and miR675 on embryonic myogenesis. MO up‐regulates H19 but blocks its miR675 bioconversion via suppressing IGF2/AKT/KHSRP signalling axis. Myogenesis in MO embryos was impeded due to the highly accumulated H19 and blocked miR675 biogenesis.

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KHSRP

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