2. Academic Validation
  3. hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma

hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma

  • Cancer Lett. 2024 Dec 30:611:217436. doi: 10.1016/j.canlet.2024.217436.
Xianghan Chen 1,  Ruining Gong 2,  Lili Wang 3,  Ke Lei 4,  Xiaolan Liu 4,  Jigang Wang 3,  Mingyue Sun 4,  Ashok Kumar Saluja 5,  Qian Yu 6,  He Ren 7
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University (Air Force Medical University), Xi'an, 710032, China.
  • 2 Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Gastrointestinal Cancer Institute/Pancreatic Disease Institute, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
  • 3 Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
  • 4 Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
  • 5 Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
  • 6 Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China. Electronic address: u3004582@connect.hku.hk.
  • 7 Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Gastrointestinal Cancer Institute/Pancreatic Disease Institute, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China. Electronic address: herenrh@163.com.
PMID: 39742990 DOI: 10.1016/j.canlet.2024.217436
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly Cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events. In particular, we identified myoferlin (MYOF), a member of the ferlin family involved in membrane processes, as a functional splicing target of hnRNPLL. hnRNPLL depletion stimulates MYOF exon 17 retention to reduce the short isoform of MYOF (MYOFb) and inhibit metastasis. In contrast, hnRNPLL or MYOFb overexpression promoted pancreatic Cancer cell migration and invasion. These results suggest that hnRNPLL is a critical factor for early PDAC metastasis. hnRNPLL and MYOFb may be potential therapeutic targets for PDAC.

Keywords

Alternative splicing; Early metastasis; MYOF; Pancreatic ductal adenocarcinoma; hnRNPLL.

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