miR‑10a increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway.

Circulating tumor cells (CTCs) that are shed from the primary tumor invade the blood stream or surrounding parenchyma to form new tumors. The present study aimed to explore the underlying mechanism of cisplatin resistance in lung adenocarcinoma CTCs and provide clinical treatment guidance for lung cancer treatment. CTCs from the blood samples of 6 lung adenocarcinoma patients were treated with different concentrations of cisplatin along with A549 and H1299 cells. The sensitivity of CTCs to cisplatin was explored by detecting the inhibitory rate via CCK‑8 assay. The related molecular mechanism was investigated by western blot analysis. miR‑10a expression was detected using quantitative real‑time PCR (RT‑qPCR). The relationship between miR‑10a and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α (PIK3CA) was verified and further confirmed by luciferase reporter assay, western blotting and RT‑qPCR assay. The results revealed that CTCs exhibited lower cisplatin sensitivity than A549 and H1299 cells. Moreover, CTCs treated with cisplatin demonstrated higher miR‑10a expression and lower PIK3CA expression than that in A549 and H1299 cells (P<0.01). Expression of phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt) phosphorylation were also decreased in A549 and H1299 cells compared with CTCs after cisplatin treatment. PIK3CA is a target of miR‑10a, and both miR‑10a overexpression and PIK3CA knockdown obviously decreased the sensitivity of A549 and H1299 cells to cisplatin as well as the expression of PI3K and phosphorylation of Akt. PIK3CA overexpression attenuated the cisplatin resistance of A549 and H1299 cells induced by miR‑10a. In conclusion, miR‑10a suppressed the PI3K/Akt pathway to strengthen the resistance of CTCs to cisplatin via targeting PIK3CA, providing a new therapeutic target for lung cancer treatment.

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