An Overview of the Cytoskeleton-Associated Role of PDLIM5

Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed novel regression-based methods to analyze ribosome profiling and alternative polyadenylation data, and identified HNRNPC as a translational controller of a specific mRNA regulon. Mechanistically, HNRNPC, in concert with PABPC4, binds near to poly(A) signals, thereby governing the alternative polyadenylation of a set of mRNAs. We found that HNRNPC and PABPC4 are downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3' UTR lengthening and subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. We also found that a small molecule, previously shown to induce a distal-to-proximal poly(A) site switching, counteracts the HNRNPC-PABPC4 driven deregulation of alternative polyadenylation and decreases the metastatic lung colonization by breast cancer cells in vivo.

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“…6a). This approach nominated PDLIM5, a member of cytoskeletonassociated protein family 35 , as a robust target of this HNRNPC-mediated pathway.…”

Section: Pdlim5 Acts Downstream Of Hnrnpc To Suppress Metastasismentioning

confidence: 99%

An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus

Navickas

Asgharian

Winkler

et al. 2021

Preprint

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“…As an actin connector protein, PDLIM5 is not only involved in cytoskeletal tissue, cellular processes and organ development but is also presumed to be involved in the genesis and development of tumors 27 . PDLIM5 has been reported to play an important role in a variety of cancers, including papillary thyroid cancer, prostate cancer and non-small cell lung cancer [28][29][30] .…”

Section: Discussionmentioning

confidence: 99%

LINC02027 / MiR-625-3p /PDLIM5 Axis Inhibits The Proliferation, Migration And Invasion And Promotes Apoptosis of HCC By Inhibiting RAS-MAPK Pathway

Wang

Zhu

Ai³

et al. 2021

Preprint

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Background and Aims: Long non-coding RNAs have been shown to promote or inhibit various cancers, acting as competing endogenous RNAs for specific microRNAs. The primary objective of this research was to investigate the underlying mechanism by which the LINC02027/miR-625-3p/PDLIM5 axis affects proliferation, migration, invasion and apoptosis in hepatocellular carcinoma (HCC). Methods: The level of LINC02027 in HCC tissues and cells and its regulatory effect on the development of HCC were detected. According to the results of database prediction and qRT-PCR, the downstream microRNA and target gene were searched. Finally, HCC cells were transfected with lentivirus and used for cell function assays (in vitro) and subcutaneous tumorigenesis assay in nude mice (in vivo).Results: Downregulation of LINC02027 was detected in HCC tissues and cell lines. The knockdown or overexpression of LINC02027 increased or reduced the proliferation migration and invasion of HCC cells, and the apoptotic ability of HCC cells decreased or increased, respectively. Mechanistically, INC02027 inhibited epithelial-to-mesenchymal transition (EMT). As a ceRNA, LINC02027 inhibited the malignant ability of HCC by competitively binding to miR-625-3p to regulate the expression of PDLIM5 and the activity of RAS-MAPK pathway.Conclusion: LINC02027/miR-625-3p/PDLIM5 axis inhibits the EMT and promotes apoptosis of HCC by regulating RAS-MAPK pathway.

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“…PDLIM5 is a cytoskeleton-related protein that acts as a binding protein [22]. In neurons, PDLIM5 has been found that present at both presynaptic and postsynaptic sites [34,35].…”

Section: Discussionmentioning

confidence: 99%

A Novel Effect of PDLIM5 In α7 Nicotinic Acetylcholine Receptors Up-Regulation And Surface Expression

Li¹,

Gou²,

Wang³

et al. 2021

Preprint

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α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are expressed widely in the brain, where they contribute to a variety of behaviors including arousal and cognition, participate in a number of neurodegenerative disorders including Alzheimer’s and Parkinson’s disease, and is responsible for nicotine addiction. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated are still less well understood. Here we show that the regulation of the α7nAChRs is controlled by PDLIM5 in the endogenous PDZ domain proteins family. We find that chronic exposure to 1 μM nicotine up-regulated both α7, β2-contained nAChRs and PDLIM5 in primary cultured hippocampal neurons, and the up-regulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, the α7nAChRs and β2nAChRs display distinct patterns of expression, with α7 co-localized more with PDLIM5. Meanwhile, PDLIM5 interacts with native brain α7 but not β2 nAChRs in neurons. Moreover, knocking down of PDLIM5 in heterologous cells abolishes nicotine-induced up-regulation of α7nAChRs. In cultured hippocampal neurons, shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs mediated currents. Proteomics analysis shows PDLIM5 interacts with α7nAChRs through the PDZ domain and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in regulating α7nAChRs, which may be relevant to plastic changes in the nervous system.

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An Overview of the Cytoskeleton-Associated Role of PDLIM5

Cited by 38 publications

References 81 publications

An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus

An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus

LINC02027 / MiR-625-3p /PDLIM5 Axis Inhibits The Proliferation, Migration And Invasion And Promotes Apoptosis of HCC By Inhibiting RAS-MAPK Pathway

A Novel Effect of PDLIM5 In α7 Nicotinic Acetylcholine Receptors Up-Regulation And Surface Expression

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