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Digestive Diseases and Sciences

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19-01-2024 | Colorectal Cancer | Original Article

SOX4/HDAC2 Axis Enhances Cell Survivability and Reduces Apoptosis by Activating AKT/MAPK Signaling in Colorectal Cancer

Authors: Anupriya S, Averi Chakraborty, Srinivas Patnaik

Published in: Digestive Diseases and Sciences | Issue 3/2024

Abstract

Background

Increased SOX4 (SRY-related HMG-box) activity aids cellular transformation and metastasis. However, its specific functions and downstream targets remain to be completely elusive in colorectal cancer (CRC).

Aims

To investigate the role of SOX4 in CRC progression and the underlying mechanism.

Methods

In the current study, online available datasets of CRC patients were explored to check the expression status of SOX4. To investigate the further functions, SOX4 was overexpressed and knocked down in CRC cells. Colony formation assay, flowcytometry analysis, and MTT assay were used to check for proliferation and apoptosis. Acridine orange staining was done to check the role of SOX4 in autophagy induction. Furthermore, western blot, qRT-PCR, and bioinformatic analysis was done to elucidate the downstream molecular mechanism of SOX4.

Results

GEPIA database showed enhanced expression of SOX4 mRNA in CRC tumor, and the human protein atlas (HPA) showed strong staining of SOX4 protein in tumor when compared to the normal tissue. Ectopic expression of SOX4 enhanced colony formation ability as well as rescued cells from apoptosis. SOX4 overexpressed cells showed the formation of acidic vesicular organelles (AVOs) which indicated autophagy. Further results revealed the activation of p-AKT/MAPK molecules upon overexpression of SOX4. SOX4 expression was found to be positively correlated with histone deacetylase 2 (HDAC2). Knockdown of SOX4 or HDAC2 inhibition induced apoptosis, revealed by decrease in BCL2 and increase in BAX expression, and inactivated the p-AKT/MAPK signaling.

Conclusion

The study uncovers that SOX4/HDAC2 axis improves cell survivability and reduces apoptosis via activation of the p-AKT/MAPK pathway.

Graphical Abstract

Available only for authorised users

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Title: SOX4/HDAC2 Axis Enhances Cell Survivability and Reduces Apoptosis by Activating AKT/MAPK Signaling in Colorectal Cancer
Authors: Anupriya S
Averi Chakraborty
Srinivas Patnaik
Publication date: 19-01-2024
Publisher: Springer US
Keywords: Colorectal Cancer
Colorectal Cancer
Valproate
Published in: Digestive Diseases and Sciences / Issue 3/2024
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-023-08215-6

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