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Peer-reviewedCC BY 4.0Advanced Science

LncRNA FLJ20021 Restrains Fibroblast Senescence and Matrix Remodeling in Pelvic Organ Prolapse by Promoting XRCC6‐Dependent ADI1 Transcription

  • YanFeng Yang1,2,3
  • BingJie Rui2,3,4
  • GuangHai Rui1
  • YiNan Duan5
  • Ji Hyang Kim3,6
6 affiliations
  1. 1Department of Obstetrics and Gynecology Fushun Maternal and Child Health Hospital Fushun China
  2. 2Department of Obstetrics and Gynecology Shengjing Hospital of China Medical University Shenyang China
  3. 3Department of Obstetrics and Gynecology CHA University School of Medicine Pocheon Republic of Korea
  4. 4Department of Obstetrics and Gynecology Fushun Second Hospital Fushun China
  5. 5Department of Gynecology Liaoning Provincial Maternal and Child Health Hospital Shenyang Liaoning China
  6. 6Fertility Center CHA University Bundang Medical Center CHA University Seongnam Republic of Korea
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Abstract

Pelvic‐organ prolapse (POP) is an age‐associated disorder that is often accompanied by uterosacral ligament (USL) weakening and extracellular matrix (ECM) degradation; however, the upstream regulators linking fibroblast aging to ECM remodeling remain incompletely defined. Here, we identify an uncharacterized long non‐coding RNA (lncRNA), FLJ20021, as significantly downregulated in POP‐derived USL tissues and primary human uterosacral‐ligament fibroblasts (hUSLFs) compared with non‐POP controls. FLJ20021 depletion reduces hUSLF proliferation and increases apoptosis and senescence, whereas FLJ20021 overexpression reverses these effects and shifts ECM‐related markers toward a matrix‐preserving profile. Mechanistically, FLJ20021 directly binds the DNA‐binding domain (DBD) of X‐ray repair cross‐complementing 6 (XRCC6), facilitates XRCC6 occupancy at the ADI1 promoter, and promotes XRCC6‐dependent ADI1 transcription. Gain‐ and loss‐of‐function as well as rescue experiments place XRCC6 downstream of FLJ20021 and support ADI1 as a required effector for FLJ20021‐dependent cellular and ECM‐related phenotypes. In POP‐relevant murine injury models, XRCC6 and ADI1 are coordinately reduced with ECM‐marker imbalance, and FLJ20021 overexpression partially restores ADI1 and ECM‐related readouts in vivo. Together, these data support a model in which FLJ20021 interacts with XRCC6 to regulate ADI1 expression, thereby linking fibroblast‐fate control to ECM homeostasis and providing mechanistic insight into POP‐associated tissue degeneration.

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Cite

BibTeXRIS
BibTeX
@article{yang2026lncrna,
  title = {{LncRNA FLJ20021 Restrains Fibroblast Senescence and Matrix Remodeling in Pelvic Organ Prolapse by Promoting XRCC6‐Dependent ADI1 Transcription}},
  author = {YanFeng Yang and BingJie Rui and GuangHai Rui and YiNan Duan and Ji Hyang Kim},
  journal = {Advanced Science},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78346},
  url = {https://doi.org/10.1002/advs.78346},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - LncRNA FLJ20021 Restrains Fibroblast Senescence and Matrix Remodeling in Pelvic Organ Prolapse by Promoting XRCC6‐Dependent ADI1 Transcription
AU  - YanFeng Yang
AU  - BingJie Rui
AU  - GuangHai Rui
AU  - YiNan Duan
AU  - Ji Hyang Kim
PY  - 2026
DA  - 2026/10/25
JO  - Advanced Science
DO  - 10.1002/advs.78346
UR  - https://doi.org/10.1002/advs.78346
AB  - Pelvic‐organ prolapse (POP) is an age‐associated disorder that is often accompanied by uterosacral ligament (USL) weakening and extracellular matrix (ECM) degradation; however, the upstream regulators linking fibroblast aging to ECM remodeling remain incompletely defined. Here, we identify an uncharacterized long non‐coding RNA (lncRNA), FLJ20021, as significantly downregulated in POP‐derived USL tissues and primary human uterosacral‐ligament fibroblasts (hUSLFs) compared with non‐POP controls. FLJ20021 depletion reduces hUSLF proliferation and increases apoptosis and senescence, whereas FLJ20021 overexpression reverses these effects and shifts ECM‐related markers toward a matrix‐preserving profile. Mechanistically, FLJ20021 directly binds the DNA‐binding domain (DBD) of X‐ray repair cross‐complementing 6 (XRCC6), facilitates XRCC6 occupancy at the ADI1 promoter, and promotes XRCC6‐dependent ADI1 transcription. Gain‐ and loss‐of‐function as well as rescue experiments place XRCC6 downstream of FLJ20021 and support ADI1 as a required effector for FLJ20021‐dependent cellular and ECM‐related phenotypes. In POP‐relevant murine injury models, XRCC6 and ADI1 are coordinately reduced with ECM‐marker imbalance, and FLJ20021 overexpression partially restores ADI1 and ECM‐related readouts in vivo. Together, these data support a model in which FLJ20021 interacts with XRCC6 to regulate ADI1 expression, thereby linking fibroblast‐fate control to ECM homeostasis and providing mechanistic insight into POP‐associated tissue degeneration.
SN  - 2198-3844
ER  -