Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Molecular Networks of Platinum Drugs and Arsenic Trioxide and Its Interaction With microRNAs in Cancer

Shihori Tanabe
* ORCID logo ,
Eger Boonstra
ORCID logo ,
Taehun Hong
,
Sabina Quader
ORCID logo ,
Ryuichi Ono
,
Horacio Cabral
,
Kazuhiko Aoyagi
,
Hiroshi Yokozaki
ORCID logo ,
Hiroki Sasaki
Version 1 : Received: 18 May 2023 / Approved: 18 May 2023 / Online: 18 May 2023 (08:41:46 CEST)

How to cite: Tanabe, S.; Boonstra, E.; Hong, T.; Quader, S.; Ono, R.; Cabral, H.; Aoyagi, K.; Yokozaki, H.; Sasaki, H. Molecular Networks of Platinum Drugs and Arsenic Trioxide and Its Interaction With microRNAs in Cancer. Preprints 2023, 2023051304. https://doi.org/10.20944/preprints202305.1304.v1 Tanabe, S.; Boonstra, E.; Hong, T.; Quader, S.; Ono, R.; Cabral, H.; Aoyagi, K.; Yokozaki, H.; Sasaki, H. Molecular Networks of Platinum Drugs and Arsenic Trioxide and Its Interaction With microRNAs in Cancer. Preprints 2023, 2023051304. https://doi.org/10.20944/preprints202305.1304.v1

Abstract

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

Keywords

drug resistance; cisplatin; arsenic; tumor microenvironment; microRNA; molecular pathway network

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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