Circ_0006168 Promotes the Migration, Invasion and Proliferation of Esophageal Squamous Cell Carcinoma Cells via miR-516b-5p-Dependent Regulation of XBP1

Abstract

Background Circular RNAs (circRNAs) exert important roles in carcinogenesis. Here, we aimed to uncover the working mechanism of circ_0006168 in esophageal squamous cell carcinoma (ESCC) development. Methods Western blot assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine protein and RNA expression, respectively. Wound healing assay and transwell migration assay were performed to assess cell migration ability, whereas cell invasion ability was evaluated by transwell invasion assay. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were utilized to analyze cell proliferation ability. Xenograft tumor model was utilized to assess the role of X-box binding protein 1 (XBP1) in xenograft tumor growth in vivo. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to verify intermolecular interactions. Results XBP1 silencing suppressed the migration, invasion and proliferation of ESCC cells in vitro and restrained the xenograft tumor growth in vivo. MicroRNA-516b-5p (miR-516b-5p) interacted with the 3ʹ untranslated region (3ʹUTR) of XBP1 in ESCC cells. MiR-516b-5p overexpression inhibited the proliferation and motility of ESCC cells. MiR-516b-5p was a molecular target of circ_0006168 in ESCC cells. The interference of circ_0006168 restrained the motility and proliferation of ESCC cells. Circ_0006168 acted as miR-516b-5p sponge to up-regulate XBP1 expression in ESCC cells. MiR-516b-5p silencing or the accumulation of XBP1 largely rescued the proliferation ability and motility in circ_0006168-silenced ESCC cells. Conclusion In conclusion, circ_0006168 contributed to ESCC development through promoting the proliferation and motility of ESCC cells via mediating miR-516b-5p/XBP1 axis.

Circ_ZNF778_006 promoted ESCC progression by upregulating HIF-1α expression via sponging miR-18b-5p

“…Tang R et al found that the circ_0006948 contributes to ESCC progression via regulating the microRNA-3612/LASP1 axis [22]. And Huang Y et al found that circ_0006168 can promote the migration, invasion, and proliferation of ESCC cells miR-516b-5p dependent regulation of XBP1 [23]. Our results also found that the circZNF778_006/miR-18b-5p/HIF-1α network can affect the progression of ESCC.…”

CircCNOT6L modulates alternative splicing of SLC7A11 via splicing factor SRSF2 to confer ferroptosis resistance and promote metastasis in prostate cancer

“…Dysregulation of circRNAs has been implicated in various cancers, in uencing processes such as growth invasion, vascularization, and apoptosis 26 . For instance, Huang et al demonstrated that circ_0006168 promotes tumorigenesis in esophageal squamous cell carcinoma 27 , while Wang et al showed that it inhibits the proliferation of human glioblastoma cells 28 . These ndings provide evidence for the involvement of circ_0006168 (circCNOT6L) in various types of cancer.…”

Establishment and Validation of a Ferroptosis-Related Long Non-Coding RNA Signature for Predicting the Prognosis of Stomach Adenocarcinoma

“…Through negative modulation of GSK3β ( Sun et al, 2020 ; Zhou et al, 2020 ), MYCT1 ( Pu et al, 2019 ), Fascin actin-bundling protein 1 (FSCN1) ( Ou et al, 2020 ), and TFF1( Shi et al, 2019 ), miR-632 modulated the WNT/β-catenin pathway and subsequently promoted cancer cell migration, invasion, proliferation, tube formation, and endothelial cell recruitment. MiR-516b–5p are reported to interact with ARHGAP5 ( Yang et al, 2021 ), XBP1 ( Huang et al, 2021 ), STAT3 ( Xu et al, 2020 ), ITGA11 ( Song et al, 2020 ), and AKAP2 ( Lin et al, 2020 ).…”