Potential Role of circPVT1 as a proliferative factor and treatment target in esophageal carcinoma

Abstract

Background Many circRNAs have been reported to play important roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in esophageal carcinoma (EC) remains unclear. In the current study, we investigated the potential role of circPVT1 in esophageal carcinoma. Methods Quantitative real-time PCR was performed to detect circPVT1 levels. CircPVT1-specific siRNA or plasmids were used to knock down or overexpression the target RNA. Hoechst Staining was implemented to evaluate the ratio of cell apoptosis. Transwell migration assays were carried out to study the effects of circPVT1 on esophageal squamous cell carcinoma cell invasion. RegRNA 2.0 was used for bioinformatics analysis. The expression levels of Pax-4, Pax-6, PPARα and PPAR-γ were assessed using Western blot. Results In the present study, we demonstrated a significant up-regulation of circPVT1 levels in EC tissues and cancer cell lines. The levels of circPVT1 decreased significantly when the cells were maintained to over-confluence. These results suggested a potential role for circPVT1 in cell proliferation. In addition, overexpressing circPVT1 in TE-10 cell promoted invasive ability of cancer cell. In contrast, siRNA knockdown of circPVT1 inhibited this phenomenon, leading to increased apoptosis levels of TE-10 cell. What’s more, miR-4663 had the effect of inhibiting tumor growth by downregulated Paxs and upregulated PPARs. Whereas, after the addition of circPVT1, this effect no longer worked, suggesting that circPVT1 may affect the malignancy of the tumor by affecting miRNA and regulating the levels of Paxs and PPARs. Conclusions Collectively, our study reveals a critical role for circPVT1 in esophageal carcinoma, which may provide new insights of this circRNA as a biomarker for the diagnosis and treatment target of EC.

Emerging landscape of circular RNAs as biomarkers and pivotal regulators in osteosarcoma

“…circRNA CDR1as, also known as ciRS‐7, functions as an oncogenic or suppressive regulator in multiple cancer progression and chemoresistance, such hepatocellular carcinoma (HCC; Su et al, 2019), ovarian cancer (Zhao, Ji, Wang, He, & Li, 2019), bladder cancer (Yuan et al, 2019), and nasopharyngeal carcinoma (Q. Zhong et al, 2019). Similarly, through systematic and comprehensive pan‐cancer analysis, CDR1as was proved to play a specific role in alternation of the tumor microenvironment by regulation of the TGF‐β pathway and extracellular matrix (ECM)‐receptor interaction (Zou et al, 2019).…”

“…Later, circRNA was screened and identified as a proliferative factor in gastric cancer (J. Chen et al, 2017). Subsequent studies further confirmed the oncogenic role of circPVT1 in several carcinomas, including head and neck squamous cell carcinoma (Verduci et al, 2017), acute lymphoblastic leukemia (ALL; Gaffo et al, 2019; J. Hu, Han, et al, 2018), non‐small cell lung cancer (NSCLC; S. Qin, Chang, Yuan, Huang, & Qiu, 2019), colorectal cancer (CRC; Z. Wang, Su, Xiang, Zhao, & Qin, 2019), GBM (G. Chi, Yang, Xu, & Liu, 2020) and esophageal carcinoma (R. Zhong, Chen, Mo, Li, & Zhang, 2019).…”

Circular RNAs and esophageal cancer

“…It is suggested that the level of plasma circGSK3β may be a valuable predictor of recurrence/metastasis of EC [ 37 ]. Following results showed that the expressions of circ_0000654 [ 38 ], circPVT1 [ 39 ], circ_0006168 [ 40 ], circ_0004370 [ 41 ], circ-TTC17 [ 42 ], circ_0067934 [ 43 ], circ_0006948 [ 44 ], circ_0030018 [ 45 ], circ_100876 [ 46 ], circ-DLG1 [ 47 ] and circ-SLC7A5 [ 48 ] were up-regulated in EC and related to the poor prognosis of EC. However, the other group found that the expression of circ-SMAD7 in EC was significantly down-regulated and negatively correlated with tumor stage and lymph node metastasis [ 49 ], and the low expression of circ-Foxo3 was related to poor prognosis [ 50 ].…”

“…Further studies on the mechanism have proved that circ UBAP2 might play the role of oncogenes by regulating the miR-422a/Rab10 axis of ESCC [ 55 ]. Compared with paracancerous tissues, the expressions of hsa_circ_0067934, circFNDC3B, circ-TTC17, hsa_circ_0006168, circPVT1 and hsa_circ_100873 were significantly up-regulated in EC tissues [ 39 , 40 , 42 , 43 , 56 , 57 ]. So far, cir-ITCH, circ-PRKCI, circRAD23B, cZNF292, circ-Foxo3, circGSK3 β, circLARP4 and hsa_circ_0004771 have been shown to regulate the proliferation and apoptosis of EC cells through different signal pathways [ 35 , 37 , 50 , 58 – 62 ].…”

CircPVT1 Promotes Bladder Cancer Progression by Acting as a ceRNA for miR-140-3p to Target TRPS1

“…[6][7][8][9][10] Recently, circPVT1 was shown that it could contributed to the progression of lung cancer, hepatocellular carcinoma, and Osteosarcoma. [9][10][11][12][13][14] However, the roles of circPVT1 have not been elucidated in BC.…”