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Review Open Access

Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review)

  • Authors:
    • Santosh Kumar Rai
    • Mohd Imran Khan
    • Rakesh Kumar
    • Rakesh Ishwar Patil
    • Sanjeev Dhawan
    • Amit Panwar
    • Anil Kumar
  • View Affiliations / Copyright

    Affiliations: New Drug Discovery Research, Mankind Research Centre Unit‑1, Mankind Pharma Limited, Gurugram, Haryana 122051, India
    Copyright: © Rai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 86
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    Published online on: July 17, 2025
       https://doi.org/10.3892/mco.2025.2881
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Abstract

Staphylococcal nuclease and tudor domain‑­containing protein 1 (SND1) is an oncoprotein that is overexpressed in various types of cancer, including breast, prostate, lung, colorectal and hepatocellular carcinomas, as well as malignant gliomas, especially in cases of advanced and metastatic cancer. SND1 has a significant role in tumour development via its interactions with RNA and partner proteins. SND1 functions as a nuclease within the RNA‑induced silencing complex, where small RNAs (such as siRNAs or miRNAs) bind to ribonucleoproteins to mediate RNA interference and silencing of tumour suppressor genes. Metadherin (MTDH) has been identified as an important protein partner of SND1, and the SND1‑MTDH interaction has been reported to drive tumour initiation, metastasis and immune evasion in various types of cancer. Therefore, SND1 is considered as a crucial target for cancer therapy, and multiple approaches have been explored to inhibit its nuclease activity or disrupt its interaction with MTDH. In the present review, both the oncogenic functions of SND1 and therapeutic strategies that target either its binding to RNA or its interaction with MTDH are investigated.
View Figures

Figure 1

Overall structure of the MTDH-SND1
complex. (A) Two perpendicular views are shown. The SN1 and SN2
domains of SND1 are colored cyan and magenta, respectively, while
MTDH is colored yellow. SND1 is displayed as (A) a ribbon diagram
and (C) surface representation. MTDH is depicted using a worm
(backbone) and cylinder (side chain) representation. (B) A close-up
stereo view of the MTDH-SND1 interface. (C) The MTDH peptide
(D393WNAPAEEWGN403) occupies the shallow groove between SN1 and SN2
domains, with the two tryptophan residues, W394 and W401, forming
extensive hydrophobic contacts with two well-defined hydrophobic
pockets in SND1(7). MTDH,
metadherin; SND1, staphylococcal nuclease and tudor
domain-containing protein 1.

Figure 2

SND1 domains and related functions.
SND1, staphylococcal nuclease and tudor domain-containing protein
1.

Figure 3

Overall mechanism and role of SND1 in
cancer: (1) SND1 role in
RNA-related processing and gene regulation. (2) SND1 role in genomic stability and
chromatin remodelling. (3) SND1
role in immune evasion and (4)
SND1 role in metastasis and invasion. SND1, staphylococcal nuclease
and tudor domain-containing protein 1; MTDH, metadherin; MHC1,
major histocompatibility complex I; DrP1, dynamin-related protein
1; KDM6A, lysine demethylase 6A; ERG, ETS transcription factor.

Figure 4

Therapeutic approaches for targeting
of SND1. SND1, staphylococcal nuclease and tudor domain-containing
protein 1; MTDH, metadherin; pdTp, 3',5'-deoxythymidine
bisphosphate.

Figure 5

Inhibitors reported to inhibit
nuclease activity or RNA binding of SND1.

Figure 6

Small molecule inhibitors reported to
inhibit SND1 interaction with partner proteins.

Figure 7

Peptide inhibitors reported to
inhibit SND1-MTDH protein-protein interaction.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Rai SK, Khan MI, Kumar R, Patil RI, Dhawan S, Panwar A and Kumar A: Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review). Mol Clin Oncol 23: 86, 2025.
APA
Rai, S.K., Khan, M.I., Kumar, R., Patil, R.I., Dhawan, S., Panwar, A., & Kumar, A. (2025). Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review). Molecular and Clinical Oncology, 23, 86. https://doi.org/10.3892/mco.2025.2881
MLA
Rai, S. K., Khan, M. I., Kumar, R., Patil, R. I., Dhawan, S., Panwar, A., Kumar, A."Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review)". Molecular and Clinical Oncology 23.4 (2025): 86.
Chicago
Rai, S. K., Khan, M. I., Kumar, R., Patil, R. I., Dhawan, S., Panwar, A., Kumar, A."Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review)". Molecular and Clinical Oncology 23, no. 4 (2025): 86. https://doi.org/10.3892/mco.2025.2881
Copy and paste a formatted citation
x
Spandidos Publications style
Rai SK, Khan MI, Kumar R, Patil RI, Dhawan S, Panwar A and Kumar A: Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review). Mol Clin Oncol 23: 86, 2025.
APA
Rai, S.K., Khan, M.I., Kumar, R., Patil, R.I., Dhawan, S., Panwar, A., & Kumar, A. (2025). Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review). Molecular and Clinical Oncology, 23, 86. https://doi.org/10.3892/mco.2025.2881
MLA
Rai, S. K., Khan, M. I., Kumar, R., Patil, R. I., Dhawan, S., Panwar, A., Kumar, A."Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review)". Molecular and Clinical Oncology 23.4 (2025): 86.
Chicago
Rai, S. K., Khan, M. I., Kumar, R., Patil, R. I., Dhawan, S., Panwar, A., Kumar, A."Staphylococcal nuclease and tudor domain‑containing protein 1: An emerging therapeutic target in cancer (Review)". Molecular and Clinical Oncology 23, no. 4 (2025): 86. https://doi.org/10.3892/mco.2025.2881
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