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2 results on '"Jahyun Oh"'

1. Hexokinase 2 is a molecular bridge linking telomerase and autophagy.

Author

Jae-Il Roh, Yujin Kim, Jahyun Oh, Yunmi Kim, Jeehyun Lee, Jaehoon Lee, Kyung-Hee Chun, and Han-Woong Lee

Subjects
Medicine, Science
Abstract

Autophagy is systematically regulated by upstream factors and nutrients. Recent studies reported that telomerase and hexokinase 2 [HK2) regulate autophagy through mTOR and that telomerase has the capacity to bind to the HK2 promoter. However, the molecular linkage among telomerase, HK2, and autophagy is not fully understood. Here, we show that HK2 connects telomerase to autophagy. HK2 inhibition in HepG2 cells suppressed TERT-induced autophagy activation and further enhancement by glucose deprivation. The HK2 downstream factor mTOR was responsible for the TERT-induced autophagy activation under glucose deprivation, implying that TERT promotes autophagy through an HK2-mTOR pathway. TERC played a role similar to that of TERT, and simultaneous expression of TERT and TERC synergistically enhanced HK2 expression and autophagy. At the gene level, TERT bound to the HK2 promoter at a specific region harboring the telomerase-responsive sequence 'TTGGG.' Mutagenesis of TERC and the TERT-responsive element in the HK2 promoter revealed that TERC is required for the binding of TERT to the HK2 promoter. We demonstrate the existence of a telomerase-HK2-mTOR-autophagy axis and suggest that inhibition of the interaction between telomerase and the HK2 promoter diminishes glucose starvation-induced autophagy.

Published
2018
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2. Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer

Author

Young-Hoon Sung, Seungeon Lee, Yaechan Song, Do Young Hyeon, Jae-Hoon Lee, Yujin Kim, Jae-il Roh, Hye Jeong Kim, Bomin Park, Yonghwan Kim, Taewook Nam, Jahyun Oh, Han Woong Lee, Daehee Hwang, and Sushil Devkota

Subjects
0301 basic medicine, Cancer Research, Lung Neoplasms, Microarray, Cell, Cell Cycle Proteins, Biology, medicine.disease_cause, Models, Biological, Article, Proto-Oncogene Proteins p21(ras), Mice, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Biomarkers, Tumor, Genetics, medicine, Animals, Humans, Lung cancer, neoplasms, Molecular Biology, Protein kinase B, Cell Proliferation, Mice, Knockout, Tissue microarray, Cell growth, Prognosis, medicine.disease, respiratory tract diseases, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Cell Transformation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, Cancer research, KRAS, Carcinogenesis, Proto-Oncogene Proteins c-akt, Non-small-cell lung cancer, Signal Transduction, Cell signalling
Abstract

KRAS-mutant non-small cell lung cancer (NSCLC) is a major lung cancer subtype that leads to many cancer-related deaths worldwide. Although numerous studies on KRAS-mutant type NSCLC have been conducted, new oncogenic or tumor suppressive genes need to be detected because a large proportion of NSCLC patients does not respond to currently used therapeutics. Here, we show the tumor-promoting function of a cell cycle-related protein, PIERCE1, in KRAS-mutant NSCLC. Mechanistically, PIERCE1 depletion inhibits cell growth and AKT phosphorylation (pAKT) at S473, which is particularly observed in KRAS-mutant lung cancers. Analyses of AKT-related genes using microarray, immunoblotting, and real-time quantitative PCR indicated that PIERCE1 negatively regulates the gene expression of the AKT suppressor, TRIB3, through the CHOP pathway, which is a key regulatory pathway for TRIB3 expression. Similarly, in vivo analyses of PIERCE1 depletion in the KRAS mutation-related lung cancer mouse models revealed the suppressive effect of PIERCE1 knockout in urethane- and KRASG12D-induced lung tumorigenesis with decreased pAKT levels observed in the tumors. Tissue microarrays of human lung cancers indicated the expression of PIERCE1 in 83% of lung cancers and its correlation with pAKT expression. Thus, we illustrate how PIERCE1 depletion may serve as a therapeutic strategy against KRAS-mutant NSCLC and propose the clinical benefit of PIERCE1.

Published
2020
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