Circ_0072083 interference enhances growth-inhibiting effects of cisplatin in non-small-cell lung cancer cells via miR-545-3p/CBLL1 axis

Abstract

Background: Non-small-cell lung cancer (NSCLC) is one of the common cancers in the world. Circular RNA 0072083 (circ_0072083, circZFR) has been reported to be associated with the progression of NSCLC. In this study, we intended to explore the role and the potential mechanism of circ_0072083 in NSCLC. Methods: Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_0072083, its matching linear RNA (zinc finger RNA binding protein (ZFR)) and microRNA-545-3p (miR-545-3p) in NSCLC cells. The ability of colony formation in NSCLC cells was detected by colony formation assay. The apoptosis and cell cycle were measured by flow cytometry. The metastasis was determined by transwell migration and invasion assays. The protein expression of E-cadherin, N-cadherin, Vimentin and Cbl proto-oncogene like 1 (CBLL1) was examined by western blot assay. The interaction between miR-545-3p and circ_0072083 or CBLL1 was predicted by starBase or Targetscan software. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate these interactions. Nude mice bearing tumors were used to confirm the role of circ_0072083 and cisplatin (DDP) in vivo. Results: The level of circ_0072083 was higher in NSCLC tissues and cells relative to that in adjacent non-tumor tissues and normal lung cells. The transfection of si-circ_0072083 inhibited colony formation, cell cycle and metastasis while promoted the apoptosis of NSCLC cells stimulated by DDP. MiR-545-3p was a direct functional target of circ_0072083 in NSCLC cells. CBLL1 could bind to miR-545-3p in NSCLC cells. Circ_0072083 promoted the progression of NSCLC induced by DDP through sponging miR-545-3p and enhancing the enrichment of CBLL1 in vivo and in vitro. Conclusion: Circ_0072083 depletion contributed to DDP-triggered inhibition of NSCLC tumor through miR-545-3p/ CBLL1 axis.

The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex

“…reported that circZFR promoted hepatocellular carcinoma cell proliferation through regulating miR-522/AKT1 [35]. Li et al reported that the growth of non-small-cell lung cancer could be inhibited after interfering circZFR [36]. But the effect of circZFR in cervical cancer has not been reported.…”

Circ_ZFR contributes to the paclitaxel resistance and progression of non-small cell lung cancer by upregulating KPNA4 through sponging miR-195-5p

“…As for circ_ZFR, Zhang et al disclosed that circ_ZFR was enhanced in NSCLC tissues and cells, and promoted NSCLC cell growth and metastasis by modulation of miR-101-3p/CUL4B axis [ 26 ]. Li et al unraveled that circ_0072083 interference repressed DDP resistance, cell colony formation, cell cycle and metastasis and facilitated apoptosis in NSCLC cells by regulating miR-545-3p/CBLL1 axis [ 15 ]. Herein, high level of circ_ZFR was detected in chemoresistant NSCLC tissues and cells.…”

“…Moreover, circ_0011292 improved PTX resistance in NSCLC by regulating miR-379-5p/tripartite motif-containing protein 65 (TRIM65) axis [ 14 ]. As for circ_ZFR (also termed as circ_0072083), Li et al [ 15 ] claimed that circ_ZFR deficiency could enhance the inhibition of tumor growth induced by cisplatin (DDP) in NSCLC via modulation of miR-545-3p/CBLL1 axis. However, the contributions of circ_ZFR to PTX resistance of NSCLC remain largely unexplored.…”

Warburg Effect-Promoted Exosomal Circ_0072083 Releasing Up-Regulates Nango Expression Through Multiple Pathways and Enhances Temozolomide Resistance in Glioma

“…Moreover, Wei et al reported that circ_0072083 could contribute to cell proliferation and invasion via regulating miR-1261/C8orf4 axis in papillary thyroid carcinoma [12]. In addition, circ_0072083 could promote cell proliferation, migration and invasion via regulating miR-101-3p/cullin 4B (CUL4B) [33], and facilitated cisplatin resistance via regulating miR-545-3p/Cbl proto-oncogene like 1 (CBLL1) in non-small cell lung cancer [34]. These reports indicated that circ_0072083 is a multifunctional circRNA in different tumors due to the varying tumor microenvironment.…”