Circ_0031242 Silencing Mitigates the Progression and Drug Resistance in DDP-Resistant Hepatoma Cells by the miR-924/POU3F2 Axis

Abstract

Background: Circular RNAs (circRNAs) have been implicated in the progression and chemoresistance development of hepatocellular carcinoma (HCC). However, the precise parts of circ_0031242 in HCC chemoresistance are still not fully understood. Methods: The levels of circ_0031242, miR-924 and POU class 3 homeobox 2 (POU3F2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay or Western blot analysis. IC 50 value for cisplatin (DDP) and cell viability were measured by the cell counting kit-8 (CCK-8) assay. Cell migration, invasion and apoptosis were assessed by transwell assay and flow cytometry, respectively. Targeted correlations among circ_0031242, miR-924 and POU3F2 were verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: Our data revealed that circ_0031242 was associated with HCC resistance to DDP. The silencing of circ_0031242 diminished DDP resistance, suppressed cell viability, migration, invasion and promoted apoptosis of DDP-resistant HCC cells (Huh7-R and SNU-387-R) in vitro, as well as enhanced DDP sensitivity in vivo. Mechanistically, circ_0031242 directly interacted with miR-924 by binding to miR-924. Moreover, miR-924 was a downstream effector of circ_0031242 function. POU3F2 was a direct target of miR-924, and miR-924 overexpression regulated DDP-resistant HCC cell progression and DDP resistance by down-regulating POU3F2. Furthermore, circ_0031242 modulated POU3F2 expression through sponging miR-924. Conclusion: Our findings identified that circ_0031242 functioned as an important regulator in DDP-resistant HCC cell progression and DDP resistance through the miR-924/POU3F2 axis, illuminating circ_0031242 as a potential therapeutic target for the chemoresistant HCC.

Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors

“…They found that the miR-924/POU3F2 axis could be regulated to promote the cisplatin resistance, proliferation, and invasion of hepatoma cells by circ_0031242. The same results were observed in xenografts ( Fan et al, 2021 ). The upregulation of the circ_0000517 expression in cisplatin-resistant hepatocellular carcinoma cells could promote cell cycle arrest and apoptosis through the miR-328-3P/ARID4B axis.…”

Circ_0006006 facilitates non‐small cell lung cancer progression by modulating miR‐924/SRSF7 axis

“…For example, miR‐924 was found to be abnormally expressed in hepatocellular cancer and inhibited the metastasis of hepatocellular cancer cells 32 . Moreover, miR‐924 was expressed to a low extent in hepatoma cells and suppressed cisplatin resistance, which acted as a downstream gene of circ_0031242 in hepatoma progression 33 . In NSCLC, miR‐924 exerted a tumor‐suppressive action, repressing the metastasis and multiplication of H1299 and A549 cells 18 .…”

“…32 Moreover, miR-924 was expressed to a low extent in hepatoma cells and suppressed cisplatin resistance, which acted as a downstream gene of circ_0031242 in hepatoma progression. 33 In NSCLC, miR-924 exerted a tumor-suppressive action, repressing the metastasis and multiplication of H1299 and A549 cells. 18 Consistently, low expression miR-924 in NSCLC tissues and cells was also found in the present study, and circ_0006006 acted as a sponge for miR-924, thereby regulating its expression.…”

Circular RNAs in hepatocellular carcinoma: Recent advances

“…Current studies have confirmed that circRNAs impact HCC cisplatin resistance. For example, circ_0031242 enhances cisplatin resistance in HCC by sponging miR-924 to enhance the expression of POU class 3 homeobox 2, a promoter of tumor progression and metastasis[ 112 , 113 ]. Additionally, pyruvate dehydrogenase kinase 1 (PDK1), a glycolytic enzyme, is closely associated with chemotherapy resistance[ 114 ].…”