Circular RNA circ_0032821 contributes to oxaliplatin (OXA) resistance of gastric cancer cells by regulating SOX9 via miR
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ORIGINAL RESEARCH PAPER
Circular RNA circ_0032821 contributes to oxaliplatin (OXA) resistance of gastric cancer cells by regulating SOX9 via miR-515-5p Yanmei Zhong . Dan Wang . Yanle Ding . Guixin Tian . Bing Jiang
Received: 6 August 2020 / Accepted: 22 October 2020 Ó Springer Nature B.V. 2020
Abstract Objectives Chemoresistance is one of the major obstacles for gastric cancer (GC) treatment. Exosomemediated transfer of circular RNAs (circRNAs) is associated with the drug-resistance in GC. Circ_0032821 has been reported as an oncogene in GC. This study is designed to explore the function and mechanism of Exosomal circ_0032821 in oxaliplatin (OXA) resistance of GC. Results Circ_0032821 was highly expressed in OXA-resistant GC cells, and exosomes secreted by OXA-resistant GC cells. Moreover, circ_0032821containing exosomes secreted by OXA-resistant GC cells could boost OXA resistance, proliferation, migration, and invasion in OXA-sensitive GC cells. The mechanical analysis discovered that circ_0032821 acted as a sponge of miR-515-5p to regulate SOX9 expression. Circ_0032821 silencing and OXA treatment repressed tumor growth in the GC mice model. Conclusions Exosomal circ_0032821 boosted OXA resistance of GC cells partly by the miR-515-5p/SOX9 Y. Zhong D. Wang Y. Ding B. Jiang (&) Department of Gastroenterology, Weifang People’s Hospital, No. 151, Guangwen Street, Kuiwen District, Weifang 261041, Shandong, China e-mail: [email protected] G. Tian Department of Internal Medicine, Changle County Tangwu Town Hospital, Weifang, Shandong, China
axis, hinting a promising therapeutic target for GC treatment. Keywords Circ_0032821 MiR-515-5p SOX9 Exosome Oxaliplatin Gastric cancer
Introduction Gastric cancer (GC) is the most common cancer of the digestive system, ranking second in cancer-related deaths over the world (Bray et al. 2018). Owing to no specific early symptoms, most patients with GC are often diagnosed at an advanced stage with a poor prognosis. Interestingly, oxaliplation (OXA), the newest platinum derivative in standard chemotherapy, has displayed the specific properties of high efficiency and low toxicity (Sanderson et al. 1996; Yang et al. 2006). Unfortunately, neonatal and acquired OXA resistance is still a major cause of GC treatment failure. Hence, to seek effective therapeutic targets that can sensitize GC to OXA, it is urgent to elucidate the molecular mechanism of drug resistance in GC. Over the last decade, circular RNA (circRNA), a closed RNA transcript, has been reported as an important mediator in the occurrence and development of diverse cancers. It is becoming increasingly apparent that abnormality of circRNAs is related to the development of chemo-resistance in various tumors,
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including GC. The upregulation of circFBXO11 promoted proliferation, cycle progress, and OXA resistance in hepatocellular carcinoma (Li et al. 2020b). Moreover, the enrichment of circRNA AKT3 enhanced cellular resistance to cisplati
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