[Frontiers in Bioscience, Landmark, 25, 948-960, March 1, 2020]

PCAT1/miR-129/ABCB1 axis confers chemoresistance in non-small cell lung cancer

Ruifen Tian1, Congjun Zhang2, Fuxing Xiong2, Huanwen Chen3

1Department of respiration, Shanxi Tumour Hospital, Taiyuan 030013, Shanxi Province, China, 2Medical Oncology, the First Affiliated Hospital of Anhui Medical University; Hefei 230022, Anhui Province, China, 3Cardiothoracic surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China


1. Abstract
2. Introduction
3. Materials and methods
    3.1. Patients and tumor tissues
    3.2. Cell culture
    3.3. Cell transfection
    3.4. Detection of cell proliferation capacity
    3.5. Cell apoptosis assay
    3.6. Luciferase reporter assay
    3.7. Western blot analysis
    3.8. Quantitative real-time polymerase chain reaction (qRT-PCR)
    3.9. Statistical analysis
4. Results
    4.1. lncRNA PCAT1 is upregulated in NSCLC tissues and cell lines
    4.2. Knockdown of PCAT1 improves the sensitivity of NSCLC cells to DDP
    4.3. PCAT1 acts as a ‘sponge’ for miR-129 in NSCLC cells
    4.4. ABCB1 upregulation by the PCAT1/miR-129 axis contributes to DDP resistance in DDP-resistant NSCLC cells
5. Discussion
6. Acknowledgments
7. References


Long noncoding RNA prostate cancer-associated transcript 1 (PCAT1) is oncogenic and causes progression of non-small cell lung cancer (NSCLC). We hypothesized that PCAT1 might be involved in the acquisition of chemoresistance of NSCLC cells to treatment with cisplatin (DDP). Here, we show that PCAT1 and ATP-binding cassette sub-family B member 1 (ABCB1) are highly expressed in NSCLC tissues and cell lines, and regulate the growth and apoptosis of these cells. Compared with those in DDP-sensitive patients, PCAT1 and ABCB1 are highly expressed in the tumors of DDP-resistant patients, and such overexpression correlates with a shorter overall survival of these patients. Knockdown of PCAT1 or upregulation of miR-129 led to apoptosis and sensitized the DDP-resistant cells to DDP. The 3’ UTR activity of PCAT1 and ABCB1, which was increased by PCAT1 overexpression, was shown to harbor an miR-129 binding site. DDP resistance is induced by elevated ABCB1 expression, which involves binding of miR-129 in DDP resistant cells. These findings suggest that the PCAT1/miR-129/ABCB1 axis may be a potential target for the treatment of DDP-resistant oat cell cancer.


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Abbeviations: Long noncoding RNA (lncRNA), prostate cancer-associated transcript 1 (PCAT1), non-small cell lung cancer (NSCLC), microRNAs (miRNAs), ATP-binding cassette sub-family B member 1 (ABCB1), cisplatin (DDP), Lung adenocarcinoma (LUAD), high mobility group box 1 (HMGB1), competitive endogenous RNA (ceRNAs).

Key Words: Chemoresistance, Non-Small Cell Lung Cancer, Prostate Cancer-Associated Transcript 1, MicroRNA-129, ATP-Binding Cassette Sub-Family B member 1

Send correspondence to: Huanwen Chen, Cardiothoracic surgery, the First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing 400016, China, Tel: 86-023-89012238, Fax: 02365102346, E-mail: chenhwcqykdx1204@163.com