Pinin Modulation Restores Chemosensitivity in SW620 and HCT-116 Colon Cancer Cells
4 affiliations
- 1Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy
- 2Unit of Translational and Precision Medicine, Meyer Children’s Hospital IRCCS, Florence, Italy
- 3Department of Experimental and Clinical Biomedical Sciences, “Mario Serio” University of Florence, Florence, Italy
- 4Department of Information Engineering, University of Florence, Florence, Italy
Abstract
Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, largely due to the emergence of resistance to standard chemotherapeutic regimens. The identification of molecular determinants of chemoresistance is therefore critical to improve patient stratification and therapeutic efficacy. Here, we investigate the functional role of Pinin (PNN), a multifunctional protein involved in RNA processing and gene regulation, in mediating chemoresistance in CRC. Methods: SW620 and HCT-116 colorectal cancer cells were used to investigate the functional role of PNN. Pnn expression was silenced by siRNA and lentiviral shRNA approaches. Cell sensitivity to 5-fluorouracil and oxaliplatin was evaluated by MTT assay, while apoptosis was assessed by Annexin V/7-AAD flow cytometry. Migration, invasion, and clonogenic capacity were analyzed using wound-healing, modified Boyden chamber, and colony formation assays. Metabolic reprogramming following Pnn depletion was characterized using Seahorse extracellular flux analysis. Transcriptomic alterations were investigated by Nanopore RNA sequencing, followed by differential gene expression, bioinformatic, and gene set enrichment analyses. Results: Pnn silencing significantly enhanced sensitivity to 5-fluorouracil and oxaliplatin in SW620 cells, as demonstrated by reduced cell viability, decreased IC50 values, and increased apoptotic responses. Transcriptomic profiling revealed extensive gene expression reprogramming, affecting pathways related to cell cycle progression, DNA damage response, and stress signaling. To corroborate these findings, Pnn-silenced HCT-116 cells were used to confirm the observed cytotoxic effects and independently validate selected differentially expressed genes identified by RNA-seq in SW620 cells. Notably, Pnn depletion induced a marked impairment of mitochondrial oxidative phosphorylation without compensatory glycolytic activation, indicating reduced metabolic flexibility under stress conditions. Functionally, Pnn silencing also decreased clonogenic capacity and invasive behavior. Conclusion: Collectively, these findings identify Pnn as a key regulator of chemoresistance and reveal its involvement in transcriptional control, metabolic adaptation, and stress response. Targeting PNN-related pathways may represent a promising therapeutic strategy to restore chemosensitivity and improve outcomes in colorectal cancer, although further validation is required.
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BibTeX
@article{alice2026pinin,
title = {{Pinin Modulation Restores Chemosensitivity in SW620 and HCT-116 Colon Cancer Cells}},
author = {Molli Alice and Buonvicino Daniela and Mattei Gianluca and Bonacchi Leonardo and Scuffi Irene and Calcagno Sara and Isoldi Giulia and Schiavone Nicola and De Logu Francesco and Magi Alberto and Lulli Matteo and Parenti Astrid and Lapucci Andrea},
journal = {Oncology Research},
year = {2026},
month = oct,
doi = {10.32604/or.2026.084313},
url = {https://doi.org/10.32604/or.2026.084313},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pinin Modulation Restores Chemosensitivity in SW620 and HCT-116 Colon Cancer Cells
AU - Molli Alice
AU - Buonvicino Daniela
AU - Mattei Gianluca
AU - Bonacchi Leonardo
AU - Scuffi Irene
AU - Calcagno Sara
AU - Isoldi Giulia
AU - Schiavone Nicola
AU - De Logu Francesco
AU - Magi Alberto
AU - Lulli Matteo
AU - Parenti Astrid
AU - Lapucci Andrea
PY - 2026
DA - 2026/10/28
JO - Oncology Research
DO - 10.32604/or.2026.084313
UR - https://doi.org/10.32604/or.2026.084313
AB - Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, largely due to the emergence of resistance to standard chemotherapeutic regimens. The identification of molecular determinants of chemoresistance is therefore critical to improve patient stratification and therapeutic efficacy. Here, we investigate the functional role of Pinin (PNN), a multifunctional protein involved in RNA processing and gene regulation, in mediating chemoresistance in CRC. Methods: SW620 and HCT-116 colorectal cancer cells were used to investigate the functional role of PNN. Pnn expression was silenced by siRNA and lentiviral shRNA approaches. Cell sensitivity to 5-fluorouracil and oxaliplatin was evaluated by MTT assay, while apoptosis was assessed by Annexin V/7-AAD flow cytometry. Migration, invasion, and clonogenic capacity were analyzed using wound-healing, modified Boyden chamber, and colony formation assays. Metabolic reprogramming following Pnn depletion was characterized using Seahorse extracellular flux analysis. Transcriptomic alterations were investigated by Nanopore RNA sequencing, followed by differential gene expression, bioinformatic, and gene set enrichment analyses. Results: Pnn silencing significantly enhanced sensitivity to 5-fluorouracil and oxaliplatin in SW620 cells, as demonstrated by reduced cell viability, decreased IC50 values, and increased apoptotic responses. Transcriptomic profiling revealed extensive gene expression reprogramming, affecting pathways related to cell cycle progression, DNA damage response, and stress signaling. To corroborate these findings, Pnn-silenced HCT-116 cells were used to confirm the observed cytotoxic effects and independently validate selected differentially expressed genes identified by RNA-seq in SW620 cells. Notably, Pnn depletion induced a marked impairment of mitochondrial oxidative phosphorylation without compensatory glycolytic activation, indicating reduced metabolic flexibility under stress conditions. Functionally, Pnn silencing also decreased clonogenic capacity and invasive behavior. Conclusion: Collectively, these findings identify Pnn as a key regulator of chemoresistance and reveal its involvement in transcriptional control, metabolic adaptation, and stress response. Targeting PNN-related pathways may represent a promising therapeutic strategy to restore chemosensitivity and improve outcomes in colorectal cancer, although further validation is required.
SN - 0965-0407
SN - 1555-3906
ER -