ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1564682
This article is part of the Research TopicAdvances in targeted therapeutics for gastrointestinal cancersView all 3 articles
SNORA13 Antisense Oligonucleotides Enhances the Therapeutical Effects of 5-Fluorouracil in Colon Adenocarcinoma
Provisionally accepted
- 1Medical Research Center, Chongqing General Hospital, Chongqing, China
- 2Chongqing University, Chongqing, China
- 3Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong Province, China
- 4China-Japan Friendship Hospital, Beijing, Beijing Municipality, China
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Small nucleolar RNAs (snoRNAs) play a significant role in ribosomal RNA modification and maintain homeostasis of protein synthesis. However, whether the snoRNA functioning could be taken advantage of for developing novel cancer therapeutical approaches was not clear. In this study, combinatorial small RNA arrays of clinical samples and data analysis from The Cancer Genome Atlas (TCGA) database indicate SNORA13 is upregulated in colorectal cancer (CRC). To investigate the role of SNORA13 in CRC, loss-of-function (LoF) study was conducted using transient antisense oligonucleotides (ASOs) transfection and SNORA13 knockout with CRISPR-Cas9 genome editing in HT29 colon adenocarcinoma cell line, and our data indicated suppressed cell proliferation and tumor growth in vitro and in vivo. Next, a combined administration of SNORA13-ASO and 5-Fluorouracil (5-FU) was performed in nude mice xenograft model, and our data revealed a synergistic antitumor effect of SNORA13-ASO and 5-FU. Transcriptome and translatome were conducted and the data analysis indicated knockdown of SNORA13 markedly represses translation efficiency. Moreover, both transcriptomic and proteomic analyses revealed a significant reduction of a well-characterized anti-cancer target, NNMT (Nicotinamide Nmethyltransferase), in the HT29-SNORA13-KO cells. Together, our study revealed SNORA13 is highly expressed in CRC and demonstrated knockdown of SNORA13,especially combined with 5-FU administration, is a potential optimal therapeutic approach for the treatment of CRC.
Keywords: SNORA13, 5-fluorouracil, colorectal cancer, translation efficiency, Nicotinamide N-Methyltransferase
Received: 07 Apr 2025; Accepted: 16 May 2025.
Copyright: © 2025 Wang, An, Zhang, Lyu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qing Rex Lyu, Medical Research Center, Chongqing General Hospital, Chongqing, China
Zhe Zhang, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China
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