<p>Circ_0046599 Promotes the Development of Hepatocellular Carcinoma by Regulating the miR-1258/RPN2 Network</p>

Abstract

Background Many studies have confirmed that circular RNAs (circRNAs) play a key role in the biological progression of cancers. However, the function of a novel circRNA, circ_0046599, in hepatocellular carcinoma (HCC) progression has not been explored. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of circ_0046599, microRNA (miR)-1258 and Ribophorin II (RPN2). Subcellular fractionation location assay was used to localize circ_0046599 in HCC cells. The circular characteristic of circ_0046599 was verified using Ribonuclease R (RNase R) digestion assay. Besides, cell counting kit 8 (CCK8) assay, colony formation assay, wound healing assay and transwell assay were used to detect cell proliferation, migration and invasion, respectively. The lactate production and glucose level were determined by Lactate and Glucose Assay Kits. Furthermore, the protein levels of glycolysis, metastasis and proliferation-related marker proteins, as well as RPN2 were tested by Western blot (WB) analysis. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to confirm the interactions among circ_0046599, miR-1258 and RPN2. In addition, mice xenograft models were applied to observe the effect of circ_0046599 silencing on HCC tumor growth in vivo. Results Circ_0046599 was highly expressed in HCC tissues and cells, and its knockdown could suppress HCC cell proliferation, migration, invasion and glycolysis process. MiR-1258 could be targeted by circ_0046599, and its inhibitor could invert the suppressing effect of circ_0046599 knockdown on HCC progression. Further, RPN2 was a target of miR-1258. Overexpressed RPN2 could reverse the inhibiting effect of miR-1258 overexpression on HCC progression. Also, knockdown of circ_0046599 could restrain HCC tumor growth in vivo. Conclusion Our results provided new evidence that circ_0046599 could promote the progression of HCC by increasing RPN2 expression via sponging miR-1258.

RPNs Levels Are Prognostic and Diagnostic Markers for Hepatocellular Carcinoma

“…RPN2 may precisely interact with STAT3 and NF- κ B pathways. Circ_0046599 also promoted HCC development by influencing RPN2 [ 33 ]. Moreover, RPN2 can be detected in blood exosomes [ 45 ] and urinary exosomes [ 46 ], expanding its application in diagnosis.…”

Circ_0011232 contributes to hepatocellular carcinoma progression through miR‐503‐5p/AKT3 axis

“…Previous studies have shown that circRNAs play vital roles in the carcinogenesis through a competing endogenous RNA mechanism; e.g., circ_0046599 promoted HCC cell growth, glycolysis and motility by modulating miR-1258/RPN2 axis. 26 Circ_0000517 facilitated cell viability, colony formation, cell cycle processes, and repressed apoptosis in HCC cells by elevating TXNDC5 via decoying miR-1296-5p. 27 Nonetheless, the exploration of the functions of circ_0011232 pressed proliferation through targeting insulin-like growth factor type 1 receptor.…”

Circ_0072995 Promotes Proliferation and Invasion via Regulating miR-1253/EIF4A3 Signaling in HCC

“…17 Circ_0046599 initiates HCC development and promotes metastasis via miR-1258/RPN2 signaling. 18 circ_0072995 was found to promote breast cancer For personal use only.…”