OncoTargets and Therapy (Aug 2020)
Circular RNA circLPAR3 Facilitates Esophageal Squamous Cell Carcinoma Progression Through Upregulating HMGB1 via Sponging miR-375/miR-433
Abstract
Hongzhong Cheng1 ,* Wen Jiang1 ,* Zhengji Song,2 Ting Li,2 Yulian Li,2 Libin Zhang,1 Guoping Wang1 1Department of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 2Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping WangDepartment of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming City, Yunnan Province, People’s Republic of ChinaTel +86-871-63638675Email [email protected]: Circular RNAs (circRNAs) are critical regulators of many diseases, including esophageal squamous cell carcinoma (ESCC). A recent study has shown that circLPAR3 is highly expressed in ESCC, but its role and mechanism in ESCC are still unclear.Methods: The expression levels of circLPAR3, microRNA-375 (miR-375), miR-433, and high-mobility group box 1 (HMGB1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular characteristic and localization of circLPAR3 were identified by Ribonuclease R (RNase R) and nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were tested by transwell assay. Moreover, Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related protein, as well as the HMGB1 protein. Besides, mice xenograft models were constructed to assess the effect of circLPAR3 on ESCC tumor growth in vivo. In addition, dual-luciferase reporter and RNA pull-down assays were used to identify the mechanism of circLPAR3.Results: CircLPAR3 was upregulated in ESCC tissues and cells, and its high expression was related to the poor prognosis of ESCC patients. CircLPAR3 was a stable cyclic transcript, mainly located in the cytoplasm, and its knockdown hindered the proliferation, migration and invasion of ESCC cells and inhibited ESCC tumor growth in vivo. MiR-375/miR-433 could be sponged by circLPAR3, and their inhibitors could reverse the suppression effect of silenced circLPAR3 on ESCC progression. HMGB1 could be targeted by miR-375/miR-433, and its overexpression also could invert the inhibition effect of circLPAR3 knockdown on ESCC progression.Conclusion: CircLPAR3 might play an oncogenic role in ESCC through sponging miR-375/miR-433 to promote HMGB1 expression, which might provide a theoretical basis for circLPAR3 to become a biomarker for ESCC therapy.Keywords: ESCC, circLPAR3, miR-375, miR-433, HMGB1
