Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR‐494‐3p/LASP1 axis

Abstract

Background Chemoresistance is one of the major obstacles for tumor treatment. Circular RNAs (circRNAs) have been confirmed to play vital roles in chemoresistance of cancer, including esophageal squamous cell carcinoma (ESCC). We investigated the roles and mechanisms of circ_0007142 in cisplatin (DDP) resistance of ESCC. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was conducted to determine the levels of circ_0007142, DOCK1 mRNA, microRNA‐494‐3p (miR‐494‐3p) and LIM And SH3 Protein 1 (LASP1) mRNA. RNase R assay was conducted to analyze the characteristic of circ_0007142. Cell Counting Kit‐8 (CCK‐8) assay was performed to evaluate IC50 of DDP. Flow cytometry analysis, 5‐ethynyl‐2’‐deoxyuridine (EdU) assay and transwell assay were carried out to examine cell apoptosis, proliferation and invasion, respectively. Dual‐luciferase reporter assay was employed to verify the association between miR‐494‐3p and circ_0007142 or LASP1. Murine xenograft assay was conducted to investigate the role of circ_0007142 in DDP resistant in vivo. The protein level of LASP1 in tumors was measured by Immunohistochemistry (IHC) analysis. Results Circ_0007142 was upregulated in DDP‐resistant ESCC tissues and cells. Circ_0007142 knockdown improved DDP sensitivity, induced cell apoptosis and hampered cell proliferation and invasion in DDP‐resistant ESCC cells. Circ_0007142 functioned as the sponge for miR‐494‐3p and miR‐494‐3p inhibition reversed the impacts of circ_0007142 knockdown on DDP resistance, cell apoptosis, proliferation, and invasion. LASP1 was a target of miR‐494‐3p, and the effects on DDP resistance, cell apoptosis, growth, and invasion mediated by LASP1 downregulation were rescued by miR‐494‐3p inhibition. Moreover, circ_0007142 knockdown enhanced DDP sensitivity in vivo. Conclusion Circ_0007142 improved DDP resistance of ESCC by upregulating LASP1 via sponging miR‐494‐3p.

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer

“…Further evidence to support the role of miR-494 in overcoming chemoresistance came from Peng and colleagues, who investigated acquired drug resistance of gastric cancer cells and demonstrated an impact of miR-494 in the recovery of chemoresistance against doxorubicin [ 79 ]. Moreover, Chang and colleagues showed that the depletion of miR-494 by a circular RNA contributes to cisplatin resistance [ 80 ]. Another possible aspect for future therapeutic considerations regarding miR-494 could be its use within combinatorial therapy strategies that can target more than one pathway of cancer cells; here, various kinase inhibitors, such as imatinib, sorafinib, trastuzumab, or osimertinib, already considered for dual therapy in CRC, would be interesting partners [ 81 , 82 , 83 , 84 ].…”

Identification of the methotrexate resistance-related diagnostic markers in osteosarcoma via adaptive total variation netNMF and multi-omics datasets

“…LASP1 is an actin-binding protein, and overexpression of LASP1 is associated with poor prognosis in patients with gastric cancer ( Keckesova et al, 2017 ). After the downregulation of LASP1 , the resistance of osteosarcoma cells to cisplatin was reduced, the IC50 decreased, and the knockdown of LASP1 could result in the inhibition of the proliferation of osteosarcoma cells ( Chang et al, 2022 ). LACTB is a mitochondrial protein that is highly expressed in skeletal muscle, heart, and liver ( Keckesova et al, 2017 ).…”

Association between circ_0004365 and cisplatin resistance in esophageal squamous cell carcinoma

“…Zou FW reported that circ_001275 was upregulated in cisplatin-resistant esophageal cancer tissues and cell lines and that circRNA_001275 promoted the proliferation of cisplatin-resistant cells ( 38 ). Chang et al found that circ_0007142 was increased in cisplatin-resistant ESCC and that silencing of circ_0007142 enhanced cisplatin sensitivity in ESCC ( 39 ).…”