2. Academic Validation
  3. L1TD1 promotes colorectal mucinous adenocarcinoma progression by enhancing ABCC3 mRNA stability

L1TD1 promotes colorectal mucinous adenocarcinoma progression by enhancing ABCC3 mRNA stability

  • Oncogene. 2026 Apr;45(12):1071-1086. doi: 10.1038/s41388-026-03716-w.
Haoqing He 1,  Jinqiang Yuan 1,  Haoran Wang 2,  Lili Chen 3,  Bingxu Liu 2,  Zhonghui Cui 1,  Yunfei Xu 4,  Guangyong Zhang 5,  Hui Yang 6
Affiliations

Affiliations

  • 1 Department of General Surgery, Key Laboratory of Metabolism and Gastrointestinal Tumor, Key Laboratory of Laparoscopic Technology, Shandong Medicine and Health Key Laboratory of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
  • 2 Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong Second Medical University, Weifang, Shandong, China.
  • 3 Department of Pathology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 4 Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China. [email protected].
  • 5 Department of General Surgery, Key Laboratory of Metabolism and Gastrointestinal Tumor, Key Laboratory of Laparoscopic Technology, Shandong Medicine and Health Key Laboratory of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. [email protected].
  • 6 Department of General Surgery, Key Laboratory of Metabolism and Gastrointestinal Tumor, Key Laboratory of Laparoscopic Technology, Shandong Medicine and Health Key Laboratory of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. [email protected].
PMID: 41776049 DOI: 10.1038/s41388-026-03716-w
Abstract

Colorectal mucinous adenocarcinoma (MAC), a distinct subtype of adenocarcinoma (AC) characterized by extracellular mucus production. However, the specific regulatory role of mucus production in MAC development remains underexplored. In this study, scRNA-seq analyses revealed that L1TD1 expression was significantly greater in MAC than in adjacent noncancerous tissues. L1TD1 is an RNA-binding protein that has been reported to regulate mRNA stability and stemness-associated transcriptional programs in Cancer cells. Further experiments confirmed that L1TD1 expression was elevated in MAC compared to normal tissues and L1TD1 promoted mucus production and accelerated tumor cell proliferation and metastasis. Mechanistically, further analysis revealed the RNA recognition motif (RRM) domain of L1TD1 binds to the 3' untranslated region (3'-UTR) of ABCC3 mRNA, thus increasing its stability. In addition, ABCC3 inhibition reversed L1TD1 overexpression-induced mucus production and MAC progression. Collectively our findings demonstrate that L1TD1 binds to the GUGU motif within ABCC3 mRNA and upregulates ABCC3 expression, which subsequently activates the MAPK signaling pathway and promotes Mucin production and accelerates MAC progression. These results also provide essential evidence for investigating the mechanisms of mucus production and tumor progression in MAC.

Figures
Products