Integrative Profiling of Alternative Splicing Induced by U2AF1 S34F Mutation in Lung Adenocarcinoma Reveals a Mechanistic Link to Mitotic Stress
Suyeon Kim1,2,4, Charny Park3,4, Yukyung Jun1,2, Sanghyuk Lee1,2, Yeonjoo Jung1,2,*, and Jaesang Kim1,2,*
1Ewha Research Center for Systems Biology (ERCSB), Seoul 03760, Korea, 2Department of Life Science, Ewha Womans University, Seoul 03760, Korea, 3Research Institute, National Cancer Center, Goyang 10408, Korea, 4These authors contributed equally to this work.
*Correspondence: (YJ); (JK)
Received April 22, 2018; Revised May 30, 2018; Accepted May 29, 2018.; Published online July 10, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (
Mutations in spliceosome components have been implicated in carcinogenesis of various types of cancer. One of the most frequently found is U2AF1 S34F missense mutation. Functional analyses of this mutation have been largely limited to hematological malignancies although the mutation is also frequently seen in other cancer types including lung adenocarcinoma (LUAD). We examined the impact of knockdown (KD) of wild type (wt) U2AF1 and ectopic expression of two splice variant S34F mutant proteins in terms of alternative splicing (AS) pattern and cell cycle progression in A549 lung cancer cells. We demonstrate that induction of distinct AS events and disruption of mitosis at distinct sub-stages result from KD and ectopic expression of the mutant proteins. Importantly, when compared with the splicing pattern seen in LUAD patients with U2AF1 S34F mutation, ectopic expression of S34F mutants but not KD was shown to result in common AS events in several genes involved in cell cycle progression. Our study thus points to an active role of U2AF1 S34F mutant protein in inducing cell cycle dysregulation and mitotic stress. In addition, alternatively spliced genes which we describe here may represent novel potential markers of lung cancer development.
Keywords: alternative splicing, lung adenocarcinoma, mitotic stress, S34F, U2AF1

Current Issue

31 July 2018 Volume 41,
Number 7, pp. 613~703

This Article

Cited By Articles
  • CrossRef (0)

Social Network Service

Indexed in

  • Science Central
  • CrossMark