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

Yuyan Wang, Tyler Gable, Mark Z. Ma, David Clark, Jun Zhao, Yi Zhang, Wei Liu, Li Mao, Yuping Mei

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)269-278
Number of pages10
JournalMolecular Therapy - Nucleic Acids
Volume6
DOIs
StatePublished - Mar 17 2017

Keywords

  • chemoresistance
  • lung cancer
  • piRNA-likes
  • sncRNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'A piRNA-like Small RNA Induces Chemoresistance to Cisplatin-Based Therapy by Inhibiting Apoptosis in Lung Squamous Cell Carcinoma'. Together they form a unique fingerprint.

Cite this