LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features

Villalonga, Elodie; Mosrin, Christine; Normand, Thierry; Girardin, Caroline; Serrano, A.; Žunar, Bojan; Doudeau, M.; Godin, F.; Bénédetti, Hélène; Vallée, Béatrice

doi:10.3390/cells12050805

Cited by 21 publications

(5 citation statements)

References 246 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7I). Cofilin, a substrate of LIMK1, can be phosphorylated to p-cofilin, which is involved in the formation of F-actin during neuronal differentiation (Yang et al 1998;Ben Zablah et al 2021;Villalonga et al 2023). Consistently, the mean F-actin intensity decreased significantly after knockdown of either the EIciLIMK1 or LIMK1 mRNA (Fig.…”

Section: Regulation Of Cirs and Eicirnas Has Functional Roles In Neur...supporting

confidence: 62%

Systematic identification and characterization of exon–intron circRNAs

Zhong,

Yang,

Wang

et al. 2024

Genome Res.

View full text Add to dashboard Cite

Exon–intron circRNAs (EIciRNAs) are a circRNA subclass with retained introns. Global features of EIciRNAs remain largely unexplored, mainly owing to the lack of bioinformatic tools. The regulation of intron retention (IR) in EIciRNAs and the associated functionality also require further investigation. We developed a framework, FEICP, which efficiently detected EIciRNAs from high-throughput sequencing (HTS) data. EIciRNAs are distinct from exonic circRNAs (EcircRNAs) in aspects such as with larger length, localization in the nucleus, high tissue specificity, and enrichment mostly in the brain. Deep learning analyses revealed that compared with regular introns, the retained introns of circRNAs (CIRs) are shorter in length, have weaker splice site strength, and have higher GC content. Compared with retained introns in linear RNAs (LIRs), CIRs are more likely to form secondary structures and show greater sequence conservation. CIRs are closer to the 5′-end, whereas LIRs are closer to the 3′-end of transcripts. EIciRNA-generating genes are more actively transcribed and associated with epigenetic marks of gene activation. Computational analyses and genome-wide CRISPR screening revealed that SRSF1 binds to CIRs and inhibits the biogenesis of most EIciRNAs. SRSF1 regulates the biogenesis ofEIciLIMK1, which enhances the expression ofLIMK1incisto boost neuronal differentiation, exemplifying EIciRNA physiological function. Overall, our study has developed the FEICP pipeline to identify EIciRNAs from HTS data, and reveals multiple features of CIRs and EIciRNAs. SRSF1 has been identified to regulate EIciRNA biogenesis. EIciRNAs and the regulation of EIciRNA biogenesis play critical roles in neuronal differentiation.

show abstract

Section: Regulation Of Cirs and Eicirnas Has Functional Roles In Neur...supporting

confidence: 62%

Systematic identification and characterization of exon–intron circRNAs

Zhong,

Yang,

Wang

et al. 2024

Genome Res.

View full text Add to dashboard Cite

show abstract

“…The top four targets that are significantly upregulated are: CCNG1 (Cyclin G1) and PHLPP2 which have both been shown to induce cell cycle arrest (57–61), GOLM1 (Golgi membrane protein 1, also known as GP73) which is a validated miR-27 target that is emerging as a key regulator of IL-6 also linked to innate immunity and RSV infection (62–66) and LIMK1 (LIM domain kinase 1, Fig 4E), a serine/threonine-protein kinase involved in remodelling of the cytoskeleton. LIMK1 has been shown to be an important host factor for many viral life cycles, including HIV, HSV-1, and Influenza virus (67–71) and LIMK1 inhibitors are currently explored as broad-spectrum antiviral drugs (72). These data suggest that the miR-27 HC targets most susceptible to miRNA inhibition in lung epithelial cells are highly relevant to viral infection.…”

Section: Resultsmentioning

confidence: 99%

RNA-RNA interactions between Respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity

Ressel

Kumar

Bermúdez-Barrientos

et al. 2023

Preprint

View full text Add to dashboard Cite

Specific viruses can sequester or inhibit miRNAs through direct RNA-RNA interactions to enable their life cycle, but we still lack comprehensive understanding of the existence and functions of such interactions in respiratory virus infections. Here we optimise the CLEAR-CLIP protocol in A549 cells and show that Respiratory syncytial virus (RSV) directly binds miR-26, miR-27, and let-7. We show a significant global up-regulation of miR-26 targets upon RSV infection as well as up-regulation of miR-27 targets involved in cell cycle regulation and immune signalling. Through genome analysis of miRNA-target reads we further show that pseudogenes which overlap transcriptional regulatory regions are functional miRNA targets. We identify and validate an interaction between miR-27 and a pseudogene-derived lncRNA that overlaps an enhancer and show that this interaction regulates expression of Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). This work demonstrates that RSV directly interacts with host miRNAs to de-regulate host gene expression and provides biochemical support for the ability of miRNAs to directly regulate gene transcription linked to immune signalling.

show abstract

“…In our study, we found that LIMK1 can promote the expression of actin in cervical cancer cells. Actin is an important part of the cytoskeleton, involved in cell movement, pseudopodia formation, and invasion [ 23 ]. Our results suggest that LIMK1 can promote the invasion and metastasis of cervical cancer cells by regulating the expression of actin.…”

Section: Discussionmentioning

confidence: 99%

LIMK1 promotes the development of cervical cancer by up-regulating the ROS/Src-FAK/cofilin signaling pathway

Jia,

Li,

et al. 2024

Aging

View full text Add to dashboard Cite

Objective: In this study, we investigated the mechanism of action of LIMK1 in cervical cancer progression. Methods: The biological role of LIMK1 in regulating the growth, invasion, and metastasis of cervical cancer was studied in SiHa, CaSki cells and nude mice tumor models. The role of LIMK1 in the growth of cervical cancer was evaluated by HE staining. The role of LIMK1 in the invasion, metastasis, and proliferation of cervical cancer was evaluated by cell scratch, Transwell, and monoclonal experiments. The interaction among LIMK1, ROS, and Src was evaluated by Western blotting. The effects of regulating ROS and p-Src expression on LIMK1 in the migration/invasion and proliferation of cervical cancer cells were evaluated through cellular functional assays. Results: Overexpression of LIMK1 promoted tumor growth in nude mice. Cell scratch, Transwell, and monoclonal experiments suggested that LIMK1 promoted the invasion, metastasis, and proliferation of cervical cancer cells. Western blotting suggested that LIMK1 can promote the expression of ROS-related proteins NOX2, NOX4, p-Src, and downstream proteins p-FAK, p-ROCK1/2, p-Cofilin-1, F-actin and inhibit the expression of p-SHP2 protein. Correction experiments showed that LIMK1 regulated the expression of p-FAK and p-Cofilin-1 proteins by regulating ROS and p-Src. Through the detection of cervical cancer cell functions, it was found that the activation of ROS and p-Src induced by LIMK1 is an early event that promotes the migration, proliferation, and invasion of cervical cancer cells. Conclusions: LIMK1 promotes the expression of F-actin and promotes the development of cervical cancer by regulating the oxidative stress/Src-mediated p-FAK/p-ROCK1/2/p-Cofilin-1 pathway.

show abstract

LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features

Cited by 21 publications

References 246 publications

Systematic identification and characterization of exon–intron circRNAs

Systematic identification and characterization of exon–intron circRNAs

RNA-RNA interactions between Respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity

LIMK1 promotes the development of cervical cancer by up-regulating the ROS/Src-FAK/cofilin signaling pathway

Contact Info

Product

Resources

About