Transcriptome analysis indicates TFEB1 and YEATS4 as regulatory transcription factors for drug resistance of ovarian cancer

Yi Rang Kim; Mi Sung Park; Ki Hwan Eum; Juhee Kim; Jeong Won Lee; Taejeong Bae; Dae Ho Lee; Jin Woo Choi

doi:10.18632/oncotarget.5208

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Research Papers:

Transcriptome analysis indicates TFEB1 and YEATS4 as regulatory transcription factors for drug resistance of ovarian cancer

Yi Rang Kim, Mi Sung Park, Ki Hwan Eum, Juhee Kim, Jeong Won Lee, Taejeong Bae, Dae Ho Lee and Jin Woo Choi _

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Oncotarget. 2015; 6:31030-31038. https://doi.org/10.18632/oncotarget.5208

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Abstract

Yi Rang Kim1,*, Mi Sung Park2,*, Ki Hwan Eum3, Juhee Kim3, Jeong Won Lee4, Taejeong Bae5, Dae Ho Lee6 and Jin Woo Choi3,7

1 Department of Hemato-Oncology, Yuseong Sun Hospital, Daejeon, Republic of Korea

2 Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea

3 Wonkwang Institute of Interfused Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Republic of Korea

4 Department of Obstetrics and Gynecology, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

5 Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

6 Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Iksan, Jeonbuk, Republic of Korea

7 Advanced Institute of Convergence Technology, Seoul National University Suwon Gyeonggi-do, Korea

* These authors have contributed equally to this work

Correspondence to:

Jin Woo Choi , email:

Keywords: cancer, transcription factor, drug resistance, bioinformatics

Received: March 31, 2015 Accepted: August 08, 2015 Published: August 17, 2015

Abstract

Ovarian cancer is an intractable disease because patients with ovarian cancer frequently develop drug resistance after long-term chemotherapy. Despite the availability of cumulative information on drug-resistant patients, strategies to reverse drug resistance have still not been established. In this study, we analyzed drug resistance-associated transcription factors (TFs) in ovarian cancer. Gene expression profiles of 15 drug-resistant and 11 drug-sensitive patients with ovarian cancer were compared. Our results showed that TFs TFEB1 and YEATS4 regulated the expression of downstream target genes. These 2 TFs have already been implicated in tumorigenesis or metastasis. To our knowledge, this is the first study to evaluate the involvement of these TFs in drug resistance of ovarian cancer. Interestingly, 70% knockdown of each of these TFs with siRNAs resulted in approximately 20%~30% recovery of drug sensitivity. Further, combination treatment of ovarian cancer cells with TFEB1 and YEATS4 siRNAs resulted in 35% reversal of drug resistance. The effect of these TFs on chemoresistance seemed to be associated with intrinsic apoptosis-related pathways, such as p53 activation, and not with the suppression of drug transport. Thus, we suggest a novel approach to reverse chemoresistance of ovarian cancer by suppressing TFEB1 and YEATS4.

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Research Papers:

Transcriptome analysis indicates TFEB1 and YEATS4 as regulatory transcription factors for drug resistance of ovarian cancer

Abstract