Oncotarget

Research Papers:

MALAT1-miR-101-SOX9 feedback loop modulates the chemo-resistance of lung cancer cell to DDP via Wnt signaling pathway

Wei Chen, Wei Zhao, Li Zhang, Lixin Wang, Jipeng Wang, Zongren Wan, Yongqing Hong and Liang Yu _

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Oncotarget. 2017; 8:94317-94329. https://doi.org/10.18632/oncotarget.21693

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Abstract

Wei Chen1, Wei Zhao2, Li Zhang3, Lixin Wang1, Jipeng Wang1, Zongren Wan1, Yongqing Hong1 and Liang Yu3

1Department of Respiratory Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, China

2Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

3Department of Hematology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, China

Correspondence to:

Liang Yu, email: yuliangha@163.com

Keywords: MALAT1, miR-101, SOX9, lung cancer, chemo-resistance

Received: June 29, 2017    Accepted: September 04, 2017    Published: October 09, 2017

ABSTRACT

Cisplatin (DDP)-based chemotherapy is a standard strategy for lung cancer, while chemoresistance remains a major therapeutic challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has important roles in regulating the proliferation, invasion and migration of lung cancer cell. High MALAT1 expression in lung cancer was related to poorer clinicopathologic features in this study. MALAT1 knockdown alone was sufficient to amplify DDP-induced repression of cell viability. MALAT1 knockdown could also sensitized DDP-resistant lung cancer cells (A549/DDP and H1299/DDP) to DDP. Further assays indicated that MALAT1 acted as a competing endogenous RNA to upregulate SOX9 expression by sponging miR-101 in DDP-resistant cancer cells, through Wnt signaling pathway. Moreover, SOX9 could bind to the promoter of MALAT1 to activate its transcription. Taken together, MALAT1, miR-101 and SOX9 form a feedback loop to enhance the chemo-resistance of lung cancer cell to DDP; this MALAT1-miR-101-SOX9 feedback loop plays an important role in the chemo-resistance of lung cancer cell to DDP and may serve as a potential target for cancer treatment.


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