title: Transcriptome analysis indicates TFEB1 and YEATS4 as regulatory transcription factors for drug resistance of ovarian cancer.
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.
authors: Department of Hemato-Oncology, Yuseong Sun Hospital, Daejeon, Republic of Korea.
authors: Yi Rang
authors: YR
authors: Kim
authors: Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
authors: Mi Sung
authors: MS
authors: Park
authors: Wonkwang Institute of Interfused Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Republic of Korea.
authors: Ki Hwan
authors: KH
authors: Eum
authors: Wonkwang Institute of Interfused Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Republic of Korea.
authors: Juhee
authors: J
authors: Kim
authors: Department of Obstetrics and Gynecology, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Jeong Won
authors: JW
authors: Lee
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Taejeong
authors: T
authors: Bae
authors: Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Iksan, Jeonbuk, Republic of Korea.
authors: Dae Ho
authors: DH
authors: Lee
authors: Wonkwang Institute of Interfused Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Republic of Korea.|Advanced Institute of Convergence Technology, Seoul National University Suwon Gyeonggi-do, Korea.
authors: Jin Woo
authors: JW
authors: Choi
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D012333:RNA, Messenger; C064972:TFEB protein, human; D014157:Transcription Factors; C109446:YEATS4 protein, human
keywords: bioinformatics; cancer; drug resistance; transcription factor