2. Academic Validation
  3. LCAT1 is an oncogenic LncRNA by stabilizing the IGF2BP2-CDC6 axis

LCAT1 is an oncogenic LncRNA by stabilizing the IGF2BP2-CDC6 axis

  • Cell Death Dis. 2022 Oct 18;13(10):877. doi: 10.1038/s41419-022-05316-4.
Juze Yang # 1,  Xinyi Qian # 1,  Qiongzi Qiu # 2,  Lingling Xu 1,  Meidie Pan 1,  Jia Li 1,  Jiayi Ren 1,  Bingjian Lu 2,  Ting Qiu 1,  Enguo Chen 1,  Kejing Ying 1,  Honghe Zhang 3 4,  Yan Lu 5 6,  Pengyuan Liu 7 8 9
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
  • 2 Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China.
  • 3 Department of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.
  • 4 Cancer center, Zhejiang University, Hangzhou, Zhejiang, 310013, China.
  • 5 Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China. yanlu76@zju.edu.cn.
  • 6 Cancer center, Zhejiang University, Hangzhou, Zhejiang, 310013, China. yanlu76@zju.edu.cn.
  • 7 Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China. pyliu@zju.edu.cn.
  • 8 Cancer center, Zhejiang University, Hangzhou, Zhejiang, 310013, China. pyliu@zju.edu.cn.
  • 9 Department of Physiology and Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. pyliu@zju.edu.cn.
  • # Contributed equally.
PMID: 36257938 DOI: 10.1038/s41419-022-05316-4
Abstract

Long non-coding RNAs (lncRNAs) is known to play vital roles in modulating tumorigenesis. We previously reported that LCAT1, a novel lncRNA, promotes the growth and metastasis of lung Cancer cells both in vitro and in vivo. However, the underlying mechanism(s) of LCAT1 as an oncogenic regulator remains elusive. Here, we showed that LCAT1 physically interacts with and stabilizes IGF2BP2, an m6A reader protein, by preventing its degradation via autolysosomes. IGF2BP2 is overexpressed in lung Cancer tissues, which is associated with poor survival of non-small cell lung Cancer patients, suggesting its oncogenic role. Biologically, IGF2BP2 depletion inhibits growth and survival as well as the migration of lung Cancer cells. Mechanistically, the LCAT1/IGF2BP2 complex increased the levels of CDC6, a key cell cycle regulator, by stabilizing its mRNA in an m6A-dependent manner. Like IGF2BP2, CDC6 is also overexpressed in lung Cancer tissues with poor patient survival, and CDC6 knockdown has oncogenic inhibitory activity. Taken together, the LCAT1-IGF2BP2-CDC6 axis appears to play a vital role in promoting the growth and migration of lung Cancer cells, and is a potential therapeutic target for lung Cancer. Importantly, our finding also highlights a previously unknown critical role of LCAT1 in m6A-dependent gene regulation by preventing autolytic degradation of IGF2BP2.

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