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

Circular RNA hsa_circ_0018189 drives non-small cell lung cancer growth by sequestering miR-656-3p and enhancing xCT expression.
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DOI:
10.1002/jcla.24714
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发表时间:
2022-11
影响因子:
2.7
通讯作者:
--
中科院分区:
医学4区
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--
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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. 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. 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. Hsa_circ_0018189 drove NSCLC growth by interacting with miR‐656‐3p and upregulating xCT. Circular RNA circCUL2 targets miR‐656‐3p and upregulates xCT expression, thereby promoting non‐small cell lung cancer progression.
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