miR-195-5p controls apoptotic cascade by regulating the XIAP/BCL2/Survivin network in colorectal cancer.
4 affiliations
- 1Laboratory of Molecular Medicine, National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Castellana Grotte, BA, Italy.
- 2Animal facility, National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Castellana Grotte, BA, Italy.
- 3Scientific Direction, National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy.
- 4Laboratory of Molecular Medicine, National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Castellana Grotte, BA, Italy. [email protected].
Abstract
Colorectal cancer (CRC) progression and therapeutic resistance are strongly associated with the ability of tumor cells to evade apoptosis through the dysregulation of key anti-apoptotic pathways. Among the molecular mechanisms involved in CRC progression, microRNAs (miRNAs) have emerged as key post-transcriptional regulators of pathways controlling tumor growth, invasion, therapeutic response, and cell survival. We previously demonstrated that miR-195-5p acts as a tumor suppressor in CRC by impairing proliferation, migration, invasion, and cell-cycle progression. However, its contribution to the regulation of apoptotic signaling remains incompletely understood. In this study, we aimed to investigate the role of miR-195-5p as a regulator of apoptotic signaling in CRC. Using membrane-based apoptosis arrays in CRC cell lines, we identified a miR-195-5p-dependent modulation of multiple apoptotic mediators, with XIAP, BCL2, and BIRC5 (Survivin) emerging as common targets across independent prediction tools. Functional validation demonstrated that miR-195-5p overexpression significantly reduced the transcript and protein levels of these anti-apoptotic factors. This molecular modulation resulted in enhanced apoptotic activity, as evidenced by increased caspase-3/7 activation, DNA fragmentation, and Annexin V-positive cell populations. Importantly, in vivo administration of miR-195-5p in an AOM/DSS mouse model confirmed the downregulation of XIAP, BCL2, and BIRC5 (Survivin) in colonic tissues, supporting its translational relevance. Overall, our findings identified miR-195-5p as a key upstream regulator of apoptosis in CRC and highlighted its potential as a promising therapeutic strategy to overcome apoptosis resistance and improve treatment outcomes.
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BibTeX
@article{piccinno2026mir1955p,
title = {{miR-195-5p controls apoptotic cascade by regulating the XIAP/BCL2/Survivin network in colorectal cancer.}},
author = {Emanuele Piccinno and Viviana Scalavino and Giusy Bianco and Gianluigi Giannelli and Grazia Serino},
journal = {Cell death discovery},
year = {2026},
month = jul,
doi = {10.1038/s41420-026-03280-y},
url = {https://europepmc.org/article/MED/42919837},
note = {CC BY},
}
RIS
TY - JOUR
TI - miR-195-5p controls apoptotic cascade by regulating the XIAP/BCL2/Survivin network in colorectal cancer.
AU - Emanuele Piccinno
AU - Viviana Scalavino
AU - Giusy Bianco
AU - Gianluigi Giannelli
AU - Grazia Serino
PY - 2026
DA - 2026/07/01
JO - Cell death discovery
DO - 10.1038/s41420-026-03280-y
UR - https://europepmc.org/article/MED/42919837
AB - Colorectal cancer (CRC) progression and therapeutic resistance are strongly associated with the ability of tumor cells to evade apoptosis through the dysregulation of key anti-apoptotic pathways. Among the molecular mechanisms involved in CRC progression, microRNAs (miRNAs) have emerged as key post-transcriptional regulators of pathways controlling tumor growth, invasion, therapeutic response, and cell survival. We previously demonstrated that miR-195-5p acts as a tumor suppressor in CRC by impairing proliferation, migration, invasion, and cell-cycle progression. However, its contribution to the regulation of apoptotic signaling remains incompletely understood. In this study, we aimed to investigate the role of miR-195-5p as a regulator of apoptotic signaling in CRC. Using membrane-based apoptosis arrays in CRC cell lines, we identified a miR-195-5p-dependent modulation of multiple apoptotic mediators, with XIAP, BCL2, and BIRC5 (Survivin) emerging as common targets across independent prediction tools. Functional validation demonstrated that miR-195-5p overexpression significantly reduced the transcript and protein levels of these anti-apoptotic factors. This molecular modulation resulted in enhanced apoptotic activity, as evidenced by increased caspase-3/7 activation, DNA fragmentation, and Annexin V-positive cell populations. Importantly, in vivo administration of miR-195-5p in an AOM/DSS mouse model confirmed the downregulation of XIAP, BCL2, and BIRC5 (Survivin) in colonic tissues, supporting its translational relevance. Overall, our findings identified miR-195-5p as a key upstream regulator of apoptosis in CRC and highlighted its potential as a promising therapeutic strategy to overcome apoptosis resistance and improve treatment outcomes.
SN - 2058-7716
ER -