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Piwi-Interacting RNA1037 Enhances Chemoresistance and Motility in Human Oral Squamous Cell Carcinoma Cells

Authors Li G, Wang X, Li C, Hu S, Niu Z, Sun Q, Sun M

Received 3 October 2019

Accepted for publication 13 November 2019

Published 4 December 2019 Volume 2019:12 Pages 10615—10627


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Gaetano Romano

Guanghui Li,* Xi Wang,* Chunmei Li,* Shuang Hu, Zhixing Niu, Qiang Sun, Minglei Sun

Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Qiang Sun; Minglei Sun
Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, Henan 450052, People’s Republic of China
Tel +86-371 6691 3345
Fax +86-371-6691 3935

Background: Piwi-interacting RNAs (piRNAs) are thought to silence transposable genetic elements. However, the functional roles of piRNAs in oral squamous cell carcinoma (OSCC) remain unelucidated. In the present study, we aimed to investigate the role of Piwi-interacting RNA 1037 (piR-1037) in chemoresistance to cisplatin (CDDP)-based chemotherapy and the oncogenic role of piR-1037 in OSCC cells.
Methods: RT-PCR was used to evaluate the levels of piR-1037 and X-linked Inhibitor of apoptosis protein (XIAP) mRNA in OSCC cell lines or tumor xenografts. Transfection of piR-1037 DNA antisense and piR-1037 RNA oligonucleotides was performed to suppress and overexpress piR-1037 in OSCC cells, respectively. A CCK8 assay was used to measure the viability or proliferation of OSCC cells. Apoptosis in OSCC cells and xenografts was determined using a TUNEL assay kit. The activity of caspase-3, caspase-8 and caspase-1 in OSCC cells was measured with colorimetric caspase assay kits. Western blot analysis was conducted to analyze XIAP expression in OSCC cells and xenograft samples. Immunoprecipitation (IP) and RNA pull-down assays were utilized to analyze the piR-1037 - XIAP interaction. Transwell assays were performed to evaluate migration and invasion of OSCC cells.
Results: CDDP treatment upregulated piR-1037 expression in OSCC cells and OSCC xenografts. Suppression of the CDDP-induced upregulation of piR-1037 expression enhanced the sensitivity of OSCC cells to CDDP. piR-1037 promoted protein expression and directly bound XIAP, a key apoptotic inhibitor that is implicated in chemoresistance. The relationship between piR-1037 and XIAP suggested that piR-1037 enhanced OSCC cell chemoresistance to CDDP at least partially through XIAP. Moreover, targeting the basal expression of piR-1037 inhibited cell motility by affecting epithelial–mesenchymal transition (EMT).
Conclusion: piR-1037 enhances the chemoresistance and motility of OSCC cells. piR-1037 promotes chemoresistance by interacting with XIAP and regulates the motility of OSCC cells by driving EMT.

Keywords: piwi-interacting RNA 1037, oral squamous cell carcinoma, cisplatin, apoptosis, X-linked inhibitor of apoptosis protein, motility

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