Circular RNA hsa_circ_0018189 drives non‐small cell lung cancer growth by sequestering miR‐656‐3p and enhancing xCT expression

Abstract

Background Non‐small cell lung cancer (NSCLC) is one of the cancers with a high mortality rate. CircRNAs have emerged as an important regulatory factor in tumorigenesis in recent years. However, the detailed regulatory mechanism of a circular RNA cullin 2 (hsa_circ_0018189; hsa_circ_0018189) is still unclear in NSCLC. Methods RNA levels of hsa_circ_0018189, microRNA (miR)‐656–3p, and Solute carrier family seven member 11 (SLC7A11, xCT) were analyzed by real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐qPCR), and protein level was assessed by Western blot and immunohistochemical assay. Enzyme‐linked immunosorbent assay was conducted to detect cell glutamine metabolism. Effects of hsa_circ_0018189 on cell proliferation, apoptosis, migration, and invasion were analyzed by corresponding assays. Luciferase reporter assay and RNA‐immunoprecipitation assay confirmed the target relationship between miR‐656‐3p and hsa_circ_0018189 or xCT. The in vivo function of hsa_circ_0018189 was verified by xenograft mouse models. Results Hsa_circ_0018189 abundance was overexpressed in NSCLC cells and samples. Deficiency of hsa_circ_0018189 lowered NSCLC cell proliferative, migrating, invading, and glutamine metabolism capacities, and hsa_circ_0018189 silencing inhibited the growth of tumors in vivo. Hsa_circ_0018189 could up‐regulate xCT by sponging miR‐656‐3p. And miR‐656‐3p downregulation or xCT overexpression partly overturned hsa_circ_0018189 knockdown or miR‐656‐3p mimic‐mediated repression of NSCLC cell malignancy. Conclusion Hsa_circ_0018189 drove NSCLC growth by interacting with miR‐656‐3p and upregulating xCT.

Silencing of long non-coding RNA SDCBP2-AS1/microRNA-656-3p/CRIM1 axis promotes ferroptosis of lung cancer cells

“…MiR-656-3p is a tumor suppressor in cancers, such as nasopharyngeal carcinoma (20), liver cancer (21), and colorectal cancer (22). In NSCLC, downregulation of miR-656-3p counteracted the suppression of cell proliferation, glycolysis, invasion, and migration induced by circular RNA 0018189 deficiency (23). Additionally, miR-656-3p impairs NSCLC cell proliferation and migration (24).…”

Research progress of circRNA in malignant tumour metabolic reprogramming

“…It has been found that multiple circRNAs can regulate SLC1A5 through their miRNA sponge role; therefore, the amino acid metabolism could be affected in non-small cell lung cancer [ 63 , 67 , 68 ], ovarian cancer [ 69 ], oesophageal cancer [ 62 ] and other cancer cells [ 70–72 ] ( Figure 4 ); and as the results, the development of malignant tumours would be promoted or inhibited. It has been found that circRNA can also promote the occurrence and development of non-small cell lung cancer by up regulating SLC7A11 of SLC family [ 73 ].

Figure 4.

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