piR-131582 suppresses lung adenocarcinoma progression by targeting USP22 and inhibiting EMT
Abstract
BackgroundPiwi-interacting RNAs (piRNAs) are increasingly recognized as important regulators in tumor biology. However, which specific piRNAs actively suppress the progression and metastasis of lung adenocarcinoma (LUAD), and the mechanisms involved, remain largely undefined. This study aimed to identify tumor-suppressive piRNAs in LUAD and clarify their functional regulatory axis.MethodsSmall RNA sequencing was used to profile piRNA expression in LUAD tissues. Gain-of-function experiments were carried out by overexpressing piR-131582 in A549 and H1299 cell lines. Colony formation assays, flow cytometry, and Transwell assays were performed to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. A mouse xenograft model was utilized to assess in vivo tumor growth. Bioinformatics prediction, combined with rescue experiments, was applied to identify and validate the downstream target of piR-131582.ResultsWe found that piR-131582 was significantly downregulated in LUAD tissues. Overexpression of piR-131582 suppressed colony formation, migration, and invasion in vitro, while promoting apoptosis. In parallel, it notably inhibited the growth of LUAD xenograft tumors in vivo. Mechanistically, piR-131582 directly targeted and degraded USP22. Re-introducing USP22 effectively reversed the anti-tumor effects induced by piR-131582, restoring the epithelial-mesenchymal transition (EMT) phenotype and reactivating EMT-related signaling pathways.ConclusionsOur results establish the piR-131582/USP22 axis as a critical tumor-suppressive node in LUAD. Restoring this natural inhibitory pathway may represent a promising direction for future therapeutic investigation in LUAD.
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BibTeX
@article{zhao2026pir131582,
title = {{piR-131582 suppresses lung adenocarcinoma progression by targeting USP22 and inhibiting EMT}},
author = {Shunjin Zhao and Tianfu Zeng and Ning Liu and Xiaoyi Tong and Demin Jiao and Qingyong Chen and Yukun Fang},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1976283},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1976283},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - piR-131582 suppresses lung adenocarcinoma progression by targeting USP22 and inhibiting EMT
AU - Shunjin Zhao
AU - Tianfu Zeng
AU - Ning Liu
AU - Xiaoyi Tong
AU - Demin Jiao
AU - Qingyong Chen
AU - Yukun Fang
PY - 2026
DA - 2026/11/06
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1976283
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1976283
AB - BackgroundPiwi-interacting RNAs (piRNAs) are increasingly recognized as important regulators in tumor biology. However, which specific piRNAs actively suppress the progression and metastasis of lung adenocarcinoma (LUAD), and the mechanisms involved, remain largely undefined. This study aimed to identify tumor-suppressive piRNAs in LUAD and clarify their functional regulatory axis.MethodsSmall RNA sequencing was used to profile piRNA expression in LUAD tissues. Gain-of-function experiments were carried out by overexpressing piR-131582 in A549 and H1299 cell lines. Colony formation assays, flow cytometry, and Transwell assays were performed to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. A mouse xenograft model was utilized to assess in vivo tumor growth. Bioinformatics prediction, combined with rescue experiments, was applied to identify and validate the downstream target of piR-131582.ResultsWe found that piR-131582 was significantly downregulated in LUAD tissues. Overexpression of piR-131582 suppressed colony formation, migration, and invasion in vitro, while promoting apoptosis. In parallel, it notably inhibited the growth of LUAD xenograft tumors in vivo. Mechanistically, piR-131582 directly targeted and degraded USP22. Re-introducing USP22 effectively reversed the anti-tumor effects induced by piR-131582, restoring the epithelial-mesenchymal transition (EMT) phenotype and reactivating EMT-related signaling pathways.ConclusionsOur results establish the piR-131582/USP22 axis as a critical tumor-suppressive node in LUAD. Restoring this natural inhibitory pathway may represent a promising direction for future therapeutic investigation in LUAD.
SN - 2234-943X
ER -