The circular RNA circ0005654 interacts with specificity protein 1 via microRNA-363 sequestration to promote gastric cancer progression

Abstract

Circular RNAs (circRNAs), a group of unique long noncoding RNAs, are involved in gastric carcinogenesis through multiple mechanisms, including interacting with microRNAs (miRNAs). Here, circ0005654, significantly upregulated in gastric cancer (GC), was chosen for further examination. circ0005654 was analyzed by RT-qPCR. The function of circ0005654 in GC cells was substantiated by loss-of-function assays. The mechanism of circ0005654 on miR-363/specificity protein 1 (sp1) axis was evaluated in GC cells by bioinformatics analysis, luciferase reporter, FISH, and ChIP assays. We observed that circ0005654 was enhanced in GC tissues and cells. Overexpression of circ0005654 was correlated with a poor long-term prognosis in patients with GC. Functionally, silencing of circ0005654 remarkably suppressed GC cell proliferation, migration and invasiveness in vitro and tumorigenesis and metastases in vivo. It was also established that circ0005654 served as a miR-363 sponge and enhanced sp1 expression. Furthermore, sp1 promoted GC carcinogenesis by regulating myc transcription to potentiate the Wnt/β-catenin pathway. In conclusion, circ0005654 expedites the GC development via miR-363/sp1/myc/Wnt/βcatenin axis and is a new biomarker for GC treatment regimen.

A novel circular RNA circ_HN1/miR-628-5p/Ecto-5’-nucleotidase competing endogenous RNA network regulates gastric cancer development

“…Yang et al . ascertained that circ_0005654 promoted specificity protein 1 expression to drive gastric cancer development via miR-363 competition [ 33 ]. Conversely, circ_LARP4 is a potent tumor-inhibitory circRNA in gastric carcinogenesis depending on its ceRNA activity [ 34 ].…”

MiR-363 suppresses the tumor growth of natural killer/T-cell lymphoma via the SIRT6/PI3K/AKT axis

“…Yet, the biological role of miRNA-363 in NKTCL progression remains poorly understood although past papers have reported its function in other carcinomas. In previous studies, miR-363 has been confirmed as a tumor-suppressive miRNA that suppresses the growth and metastasis of a variety of malignant tumors, including gastric cancer (11), breast cancer (12), multiple myeloma (13), colorectal cancer (14), and ovarian cancer (15).…”

The functional roles of the circRNA/Wnt axis in cancer

“…Some Wnt pathway-related circRNAs (circ0005654, circ-SFMBT2, circ_SMAD4, circRNA_0044516, and circHIPK3) are markedly upregulated in gastric cancer [73,159,161,195,197]. The expression of circ0005654, circ_SMAD4, circHIPK3, and circheckd1 are positively associated with a poor prognosis in patients with gastric cancer [73,[159][160][161]. Functionally, these circRNAs all contribute to promoting tumor cell proliferation in gastric cancer [73,159,161,194,195,197].…”

“…The expression of circ0005654, circ_SMAD4, circHIPK3, and circheckd1 are positively associated with a poor prognosis in patients with gastric cancer [73,[159][160][161]. Functionally, these circRNAs all contribute to promoting tumor cell proliferation in gastric cancer [73,159,161,194,195,197]. Additionally, circ0005654, circRNA_ASAP2, circ-SFMBT2, and circH-IPK3 obviously promote gastric cancer cell migration and invasion.…”

“…Circ-SFMBT2 upregulation indicates higher levels of oxidative stress in gastric cancer [195]. Mechanistically, in vitro and in vivo studies demonstrated that circ0005654 functions as a ceRNA of miR-363 to upregulate sp1 in the process of gastric cancer [159]. The level of CTNNB1 is regulated by circ-SFMBT2, a sponge of miR-1276 [73].…”