Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5p in prostate cancer

Sep 24, 2026

Uploaded by Kyle

Prostate cancer remains a leading cause of cancer-related death, and improved molecular markers are needed to predict onset and progression. The study focuses on low miR-145-5p expression in primary tumors and metastases, but unknown regulatory mechanisms. Bioinformatics and expression analyses across tumor datasets link miR-145-5p and lnc-ZNF30-3 to patient outcomes, followed by RNA pull-down, western blot, immunostaining, and wound-healing assays.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Keywords

Background

Androgen receptor signaling and clinical need

EMT program and key transcription factors

Hars Le et al. Biology Direct (2023) 18:38 [https://doi.org/10.1186/s13062-023-00393-7](https://doi.org/10.1186/s13062-023-00393-7) Biology Direct COMMENT Open Access Pro-tumorigenic role of lnc-ZNF30-3 as a sponge counteracting miR-145-5pin prostate cancer Matthieu Le Hars1†, Luis Jaime Castro-Vega2†, Fatemeh Rajabi 1,3, David Tabatadze4, Martha Romero5, Marina Pinskaya 1* and Irina Groisman 1,3* Abstract Background Prostate cancer remains one of the deadliest neoplasms in developed countries. Identification of new molecular markers that predict the onset and progression of the disease could improve its clinical management. Low miR-145-5p expression is consistently found in primary tumors and metastases, but the regulatory mechanisms governing its functions remain largely unknown. Methods Bioinformatics analysis was conducted to identify [1] a set of novel potential competing endogenous lncRNAs for sponging of miRNA-145-5p in prostate cancer and [2] miR-145-5p and other EMT-related miRNAs response elements in lnc-ZNF30-3 . Quantification of miR-145-5p, lnc-ZNF30-3, and TWIST1 expression levels in tumor tissues in RNA sequencing datasets of our and TCGA PRAD cohorts revealed a correlation with clinical outcome of prostate cancer patients. Biochemical and cell biology approaches, such as RNA pull-down, western blot, immunostaining, and wound healing assays were used for evaluation of the impact of TWIST1/miR-145/ lnc-ZNF30-3 interactions in prostate cancer cells altered in miRNA and lncRNA expression. Results We identified a few potential lncRNA sponges of miR-145-5p, including lnc-ZNF30-3 . It contains five response elements for miR-145-5p, but also other miRNAs targeting EMT transcription factors. Lnc-ZNF30-3 is significantly upregulated in prostate cancer cell lines and tumor tissues, and its high expression is correlated with poor patient prognosis. We demonstrated that lnc-ZNF30-3 is associated with AGO2 and specifically interacts with the miR-145-5p seed region. Knockdown of lnc-ZNF30-3 results in decreased migration of prostate cancer cells and downregulation of EMT drivers such as TWIST1 and ZEB1 at both the RNA and protein levels. These phenotypic and molecular features of lnc-ZNF30-3-depleted cells are partially rescued by miR-145-5p inhibition. Conclusions Collectively, our results point to lnc-ZNF30-3 as a novel competing endogenous lncRNA for miR- 145-5p and other miRNAs that target TWIST1 as well as other EMT transcription factors. Prostate cancer patients with †Equal contribution *Correspondence: Marina Pinskaya [marina.pinskaya@curie.fr](marina.pinskaya@curie.fr)[ ](marina.pinskaya@curie.fr)Irina Groisman [irina.groisman@curie.fr](irina.groisman@curie.fr) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The)[. The](http://creativecommons.org/licenses/by/4.0/. The)[ ](http://creativecommons.org/licenses/by/4.0/. The)Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/

FAQs

What molecular axis does the study examine in prostate cancer?

It examines the competing endogenous lncRNA lnc-ZNF30-3 and its regulation of miR-145-5p, connecting this axis to EMT-related transcription factors and prostate cancer behavior.

How were lnc-ZNF30-3 and miR-145-5p relationships studied?

The work used bioinformatics to identify miRNA response elements and binding potential, then measured miR-145-5p, lnc-ZNF30-3, and EMT markers in RNA sequencing cohorts, supported by RNA pull-down and protein-level assays.

What phenotypic effect occurs when lnc-ZNF30-3 is knocked down?

Knockdown of lnc-ZNF30-3 decreases prostate cancer cell migration and reduces EMT drivers such as TWIST1 and ZEB1 at RNA and protein levels.

Sep 24, 2026

Uploaded by Kyle