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Cell Physiol Biochem. 2017;43(3):1126-1139. doi: 10.1159/000481754. Epub 2017 Oct 5.

Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer.

Yang X1, Bai F1, Xu Y2, Chen Y1,2, Chen L1,2.

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Department of Medical Oncology, Jinling Hospital, Second Military Medical University, Nanjing, China.
Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.



Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells.


We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP) -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients' chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor.


Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells.


Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.


Autophagy; Beclin-1; Chemoresistance; MiR-30a-5p; Small cell lung cancer

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