circRNA hsa_circ_0005909 Predicts Poor Prognosis and Promotes the Growth, Metastasis, and Drug Resistance of Non-Small-Cell Lung Cancer via the miRNA-338-3p/SOX4 Pathway

circRNA hsa_circ_0005909 通过 miRNA-338-3p/SOX4 通路预测不良预后并促进非小细胞肺癌的生长、转移和耐药性

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作者:He-Mei Song, Dan Meng, Jin-Ping Wang, Xiao-Yan Zhang

Background

Circular RNAs (circRNAs) are powerful factors in regulating various cancer behaviors. It has been manifested in previous researches that circular RNA hsa_circ_0005909 (circ_0005909) exhibits a regulatory function in osteosarcoma. However, there are no other studies on whether circ_0005909 displays potential functions on the progression of non-small-cell lung cancer (NSCLC).

Conclusions

circ_0005909 promoted the progression of NSCLC via the modulation of the miRNA-338-3p/SOX4 axis, which may be a therapeutic target for NSCLC.

Methods

RT-PCR was applied to examine the expression of circ_0005909 in NSCLC. To study the specific behaviors of NSCLC cells after circ_0005909 knockdown, cell counting kit-8 (CCK-8) assays, colony formation assays, Transwell assays, and xenograft tumor model assays were conducted. Bioinformatics and luciferase reporter assays were employed to study the association among circ_0005909, miRNA-338-3p, and SOX4.

Results

In this research, our group firstly showed that circ_0005909 expressions were distinctly increased in NSCLC specimens and cell lines. Clinical studies revealed that high circ_0005909 expressions were associated with poor prognosis of NSCLC patients. Functionally, knockdown of circ_0005909 was observed to suppress the proliferation, metastasis, and drug resistance of NSCLC cells. In the terms of mechanism, circ_0005909 could act as a sponge of miRNA-338-3p, and miRNA-338-3p could target SOX4. In addition, miRNA-338-3p inhibitors reversed the suppressor ability of circ_0005909 silence on NSCLC behaviors. Conclusions: circ_0005909 promoted the progression of NSCLC via the modulation of the miRNA-338-3p/SOX4 axis, which may be a therapeutic target for NSCLC.

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