A piRNA-like Small RNA Induces Chemoresistance to Cisplatin-Based Therapy by Inhibiting Apoptosis in Lung Squamous Cell Carcinoma

作者：Yuyan Wang, Tyler Gable, Zsuzsanna Márk, David J. Clark, Jun Zhao, Yi Zhang, Wei Liu, Mao Li, Yuping Mei · 发表于：Molecular Therapy — Nucleic Acids · 年份：2017 · DOI：10.1016/j.omtn.2017.01.003 · 被引用次数：54 · 研究领域：Cancer Mechanisms and Therapy、Chromosomal and Genetic Variations、MicroRNA in disease regulation

Lung cancer is the leading cause of cancer-related death worldwide. Although advanced drugs have benefitted patients, therapeutic success has largely been hampered because of rapid development of resistance. Here we report that PIWI-interacting RNA likes (piR-Ls), a novel type of functional sncRNAs, play key roles in chemoresistance to cisplatin (CDDP)-based chemotherapy in lung squamous cell carcinoma (LSCC). piR-L-138 was upregulated upon CDDP-based chemotherapy both in LSCC cells and in patient-derived xenograft (PDX) LSCC models. Further, targeting upregulated piR-L-138 led to increased apoptosis in CDDP-treated LSCC cells and LSCC xenograft mice treated with CDDP. In addition, piR-L-138 directly interacted with p60-MDM2 and inhibited CDDP-activated apoptosis in p53-mutated LSCC. We identified the upregulated piR-L-138 upon CDDP-based chemotherapy, confirmed the enhanced sensitivity of LSCC to agents by targeting the upregulated piR-L-138 both in vitro and in vivo, and revealed mechanisms underlying piR-L-138 in chemoresistance, bolstering a new emerging clinical modality where novel functional piR-Ls provide potential strategies to overcome chemoresistance for patients with LSCC.