National Cheng Kung University
Benson Lab
RNA Biology and Precision Medicine
Our laboratory studies how cellular signals control the machinery that processes RNA. We focus on DGCR8, whose regulated assembly and choice of protein partners connect microRNA (miRNA) biogenesis with small nucleolar RNA (snoRNA) turnover and protein synthesis.
About our research
Using hypoxia and growth-factor signaling, we investigate how RNA-processing systems change during cellular adaptation. This work builds on our discovery of HIF-1α-dependent Dicer degradation and its contribution to metastatic progression.
Research collaborations, industry partnerships, and opportunities to join Benson Lab.
Department of Medical Laboratory Science and Biotechnology
College of Medicine, National Cheng Kung University, Tainan, Taiwan
Research Highlights
Signal-directed RNA regulation
2018 / Journal of Clinical Investigation
Selective Dicer turnover links hypoxic signaling to metastasis
HIF-1α recruits the E3 ligase Parkin to Dicer, promoting Dicer monoubiquitination and autophagic-lysosomal degradation.
Explore this finding
HIF-1α recruits the E3 ligase Parkin to Dicer, promoting Dicer monoubiquitination and autophagic-lysosomal degradation. Dicer loss impairs maturation of tumor-suppressive miRNAs. Restoring Dicer rescues miRNA maturation and target repression; restoring miR-200b suppresses epithelial-mesenchymal transition and migration and reduces liver and lung metastasis in mice. Human colon and breast tumors provide complementary evidence linking the HIF-1α/Dicer balance to disease progression. Lai et al., Journal of Clinical Investigation, 2018.
2024 / Nucleic Acids Research
DGCR8 assembly controls miRNA processing
HIF-1α preferentially binds monomeric DGCR8, limiting its dimerization and productive association with Drosha.
Explore this finding
HIF-1α preferentially binds monomeric DGCR8, limiting its dimerization and productive association with Drosha. This reduces Microprocessor assembly and pri-miRNA processing without a corresponding decrease in Drosha or DGCR8 abundance. DNA-binding-deficient HIF-1α retains this effect, supporting a role independent of transcription. The study identifies complex assembly as a regulatory control point under hypoxia and growth-factor stimulation. Li et al., Nucleic Acids Research, 2024.
2026 / Nucleic Acids Research
DGCR8 reassignment connects RNA maturation and turnover
HIF-1α redirects DGCR8 from Drosha toward RRP6-containing RNA exosome complexes, while shifting its RNA engagement from pri-miRNAs to mature snoRNAs.
Explore this finding
HIF-1α redirects DGCR8 from Drosha toward RRP6-containing RNA exosome complexes, while shifting its RNA engagement from pri-miRNAs to mature snoRNAs. DGCR8 and RRP6 redistribute from nucleoli to the nucleoplasm, and snoRNA degradation increases. DGCR8- and RRP6-dependent snoRNA loss is linked to altered ribosomal RNA modification and processing and reduced protein synthesis. This work connects reassignment of a shared RNA-processing factor to coordinated changes in RNA maturation and turnover. Li et al., Nucleic Acids Research, 2026.
RNA regulation in treatment response
In sorafenib-resistant hepatocellular carcinoma, TARBP2 loss stabilizes Nanog and supports stem-like persistence through a function separable from Dicer binding. In breast cancer, snoRNA U50A reduces c-Myc-mTOR signaling and mTOR abundance, contributing to everolimus resistance. These studies connect RNA regulation to specific mechanisms of treatment response. See Lai et al., 2019 and Li et al., 2024.
HIF-1α and RNA-processing machinery
Hypoxia and growth-factor signaling engage a transcription-independent HIF-1α program that reorganizes RNA-processing machinery.
HIF-1α binds monomeric DGCR8 to inhibit Microprocessor assembly and pri-miRNA processing (Li et al., 2024), and redirects DGCR8 from Drosha to the RRP6-containing RNA exosome, shifting RNA engagement toward mature snoRNAs (Li et al., 2026). Increased snoRNA turnover reduces rRNA modification, alters rRNA processing and lowers translation.
In the cytoplasm, HIF-1α recruits Parkin to Dicer, promoting monoubiquitination and autophagic–lysosomal degradation, thereby suppressing miRNA maturation and promoting metastasis (Lai et al., 2018).
Together, these studies establish signal-directed control of enzyme availability, complex assembly and partner choice as a mechanism linking RNA homeostasis to hypoxic adaptation.
Full figure legend and abbreviations
Figure 1. Signal-directed organization of RNA-processing machinery.
Integrated studies from Benson Lab establish transcription-independent HIF-1α control of RNA-processing machinery in response to hypoxia and growth-factor signaling. In the nucleus, HIF-1α binds monomeric DGCR8 and inhibits dimerization, reducing productive Microprocessor (MC) assembly and pri-miRNA processing (Li et al., 2024).
HIF-1α also redirects DGCR8 from Drosha toward the RRP6-containing RNA exosome complex (EC), while shifting RNA engagement from pri-miRNAs to mature snoRNAs (Li et al., 2026). Accompanied by redistribution of DGCR8 and RRP6 toward the nucleoplasm, this MC-to-EC switch enhances mature snoRNA turnover through RRP6-mediated 3′→5′ decay. The resulting snoRNA loss reduces rRNA modification, alters rRNA processing and lowers protein-synthetic output. Conservation in worms and flies, together with concordant findings in human tumors, connects DGCR8 reassignment to RNA homeostasis and biosynthetic control.
In the cytoplasm, Dicer processes exported pre-miRNAs into miRNA duplexes. HIF-1α bridges Parkin and Dicer, promoting Dicer monoubiquitination, autophagic capture and lysosomal degradation (Lai et al., 2018). Dicer loss impairs miRNA maturation; restoring Dicer rescues miRNA maturation and activity, while restoring miR-200b suppresses epithelial–mesenchymal transition, migration and experimental metastasis.
Together, these studies establish HIF-1α-directed reconfiguration of RNA machinery as a mechanism of hypoxic adaptation, linking environmental cues to RNA maturation, RNA turnover, biosynthetic output and metastatic behavior.
Faded complexes indicate reduced dimerization, assembly or association. The shaded nucleoplasmic region highlights the DGCR8–RRP6 pathway.
Abbreviations: HIF-1α, hypoxia-inducible factor 1α; MC, Microprocessor complex; EC, RNA exosome complex; pri-miRNA, primary microRNA; pre-miRNA, precursor microRNA; snoRNA, small nucleolar RNA; rRNA, ribosomal RNA; Ub, ubiquitin.
Source references
1. Lai HH, Li JN, Wang MY, Huang HY, Croce CM, Sun HL, Lyu YJ, Kang JW, Chiu CF, Hung MC, Suzuki HI, Chen PS. HIF-1α promotes autophagic proteolysis of Dicer and enhances tumor metastasis. Journal of Clinical Investigation. 2018;128(2):625–643. https://doi.org/10.1172/JCI89212
2. Li JN, Wang MY, Ruan JW, Lyu YJ, Weng YH, Brindangnanam P, Coumar MS, Chen PS. A transcription-independent role for HIF-1α in modulating microprocessor assembly. Nucleic Acids Research. 2024;52(19):11806–11821. https://doi.org/10.1093/nar/gkae792
3. Li JN, Wang MY, Lo C, Yen L, Yu CH, Lyu YJ, Chen PS. A non-canonical role for HIF-1α: redirecting DGCR8 to the RNA exosome for snoRNA degradation and translational modulation. Nucleic Acids Research. 2026;54(3):gkag070. https://doi.org/10.1093/nar/gkag070
Research Directions
Current research directions
RNA Processing & Regulation
RNA processing, cellular signals and protein synthesis.
Cancer Drug Resistance
Response and resistance to endocrine therapies (including SERDs) and CDK4/6 inhibitors.
RNA & Cancer Immunity
RNA sensing, interferon signaling and immune checkpoints.
Targeted Delivery & Engineering
Engineered receptors, recognition modules and ADC concepts.
RNA Therapeutics & Nanotechnology
DNA nanostructures for RNA regulation in cancer and pigmentation research.
Multi-Omics & Target Discovery
Integrating lab and public data to explore targets and assess priorities.
Selected Publications
Authorship roles below refer to Pai-Sheng Chen.
- Li JN, Wang MY, Lo C, Yen L, Yu CH, Lyu YJ, Chen PS. A non-canonical role for HIF-1α: redirecting DGCR8 to the RNA exosome for snoRNA degradation and translational modulation. Nucleic Acids Research. 2026;54(3):gkag070. doi:10.1093/nar/gkag070.Sole corresponding author.
- Li JN, Wang MY, Ruan JW, Lyu YJ, Weng YH, Brindangnanam P, Coumar MS, Chen PS. A transcription-independent role for HIF-1α in modulating microprocessor assembly. Nucleic Acids Research. 2024;52(19):11806–11821. doi:10.1093/nar/gkae792.Sole corresponding author.
- Lai HH, Li JN, Wang MY, Huang HY, Croce CM, Sun HL, Lyu YJ, Kang JW, Chiu CF, Hung MC, Suzuki HI, Chen PS. HIF-1α promotes autophagic proteolysis of Dicer and enhances tumor metastasis. Journal of Clinical Investigation. 2018;128(2):625–643. doi:10.1172/JCI89212.Sole corresponding author.
- Li JN, Loh ZJ, Chen HW, Lee IY, Tsai JH, Chen PS. SnoRNA U50A mediates everolimus resistance in breast cancer through mTOR downregulation. Translational Oncology. 2024;48:102062. doi:10.1016/j.tranon.2024.102062.Corresponding author.
- Lai HH, Li CW, Hong CC, Sun HY, Chiu CF, Ou DL, Chen PS. TARBP2-mediated destabilization of Nanog overcomes sorafenib resistance in hepatocellular carcinoma. Molecular Oncology. 2019;13(4):928–945. doi:10.1002/1878-0261.12449.Corresponding author.
- Shao YY, Chen PS, Lin LI, Lee BS, Ling A, Cheng AL, Hsu C, Ou DL. Low miR-10b-3p associated with sorafenib resistance in hepatocellular carcinoma. British Journal of Cancer. 2022;126(12):1806–1814. doi:10.1038/s41416-022-01759-w.First author.
- Li JN, Lin CH, Wang MY, Chen PS. Tumor hypoxia: Molecular pathways and therapeutic interventions. Drug Discovery Today. 2026;31(5):104719. Review. doi:10.1016/j.drudis.2026.104719.Corresponding author.
- Chen PS, Lo C, Ou DL, Li JN, Hsu CC, Lin CH, Wang MY. Integration of multi-omics for precision therapy in breast cancer. Drug Discovery Today. 2026;31(4):104722. Review. doi:10.1016/j.drudis.2026.104722.First author.
Teaching and Mentorship
I teach undergraduate Molecular Biology, General Biology, Clinical Microscopy with Laboratory, and Clinical Microscopy Practicum, and contribute the Regulatory RNA section of graduate-level Advanced Molecular Biology. My teaching connects molecular mechanisms with experimental reasoning and their relevance to human disease.
Current graduate students
PhD students
- Ya-Ju Yu
- Chee-Yang Tan
- Chi-Hsun Yang
- Yu-Chih Chen
Master’s students
- Ai-Xin Zhang
- Chia-Ching Hsu
- Yun-Ching Chuang
- Pei-Yu Shu
Doctoral alumni
- Jie-Ning Li (PhD, 2021) was sole first author of our 2024 and 2026 Nucleic Acids Research studies. She joined NCKU's Department of Cell Biology and Anatomy as an Assistant Professor in August 2026 and received the 2026 Young Scholar Award in Medical Research from the Professor Chen-Yuan Lee Foundation. She also joined the Early Career Researcher Editorial Board of Experimental Biology and Medicine in 2026.
- Hui-Huang Lai (PhD, 2018), sole first author of our 2018 Journal of Clinical Investigation study, is Senior Chief Manager at Microbio Co., Ltd. His doctoral work received the 2019 Lam Research Thesis Award and the 2018 Wang Ming-Ning Outstanding Paper Award in the doctoral category.
Current roles and academic service
Current Roles and Education
- Principal Investigator, Department of Medical Laboratory Science and Biotechnology, NCKU.
- CEO and Deputy Director, Research Center for Medical Laboratory Biotechnology, NCKU.
- Research Consultant, Breast Medical Center, National Cheng Kung University Hospital.
PhD, Graduate Institute of Toxicology, National Taiwan University (2009).
Postdoctoral training, Department of Oncology, National Taiwan University Hospital (2009–2012).
Academic Service
- Associate Editor — Breast Cancer Research
- Secretary-General — Taiwan Epigenetics Society
- Council Member — Toxicology Society of Taiwan
Selected Honors and Research Support
Honors
- 2025: Springer Nature Editor of Distinction: Editorial Contribution Award and Author Service Award.
- 2025: Outstanding Research Paper Award, Cheng-Hsing Medical Foundation, Taiwan.
- 2022: Ta-You Wu Memorial Award, National Science and Technology Council (NSTC), Taiwan.
- 2022: Distinguished Teaching Award and Outstanding Advisor Award, NCKU.
Research support
- 2026–2029; 2022–2025; 2014–2017: Excellent Young Scholars Project, NSTC / Ministry of Science and Technology, Taiwan.
- 2023–2026: Ta-You Wu Memorial Award Research Grant, NSTC; awarded through a separate competitive review of proposals from all eligible award recipients.
Contact
Research collaborations, industry partnerships, and joining the lab.
bio.benson@gmail.com
Phone: +886-6-2353535, ext. 6233
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University
No. 1, University Road, Tainan 701, Taiwan
