Dataset Information

FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.

ABSTRACT: Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small-molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage-inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor-targeting therapy for lung cancer.

SUBMITTER: He L

PROVIDER: S-EPMC5467497 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.

He Lingfeng L Luo Libo L Zhu Hong H Yang Huan H Zhang Yilan Y Wu Huan H Sun Hongfang H Jiang Feng F Kathera Chandra S CS Liu Lingjie L Zhuang Ziheng Z Chen Haoyan H Pan Feiyan F Hu Zhigang Z Zhang Jing J Guo Zhigang Z

Molecular oncology 20170512 6

Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that ...[more]

PMID: 28371273

Similar Datasets

Project description:BackgroundCisplatin (DDP) is among the most widely used chemotherapeutic drugs for non-small cell lung cancer (NSCLC), yet the frequent emergence of chemoresistance serves as a major barrier to the treatment of this tumor type. Long non-coding RNAs (lncRNAs) have recently been shown to influence the ability of cells to resist particular chemotherapy drugs. The present study was developed to explore the role of the lncRNA SNHG7 as a regulator of NSCLC cell chemosensitivity.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure SNHG7 expression in NSCLC tissues from patients that were sensitive/resistant to DDP, correlations between SNHG7 expression levels and the patients' clinicopathological characteristics were assessed, and the prognostic relevance of SNHG7 expression was examined via the Kaplan-Meier approach. In addition, SNHG7 expression was assessed in NSCLC cell lines that were DDP-sensitive or -resistant, while western blotting and immunofluorescence staining were employed to detect autophagy-associated protein expression in A549, A549/DDP, HCC827, and HCC827/DDP cells. NSCLC cell chemoresistance was quantified via the Cell Counting Kit-8 (CCK-8) assay approach, and flow cytometry was used to detect the apoptotic death of these tumor cells. The chemosensitivity of xenograft tumors in vivo was further assessed to validate the functional importance of SNHG7 as a regulator of NSCLC DDP resistance.ResultsRelative to paracancerous tissues, NSCLC tumors exhibited SNHG7 upregulation, and this lncRNA was further upregulated in DDP-resistant patients compared to chemosensitive patients. Consistently, higher SNHG7 expression levels were correlated with worse patient survival outcomes. DDP-resistant NSCLC cells were also found to exhibit higher levels of SNHG7 expression than chemosensitive cells, and knocking down this lncRNA enhanced the sensitivity of these cells to DDP treatment, resulting in impaired proliferation and higher rates of apoptotic death. Knocking down SNHG7 was also sufficient to suppress microtubule associated protein 1 light chain 3 beta (LC3B) and Beclin1 protein levels and promote p62 upregulation in vitro. The silencing of this lncRNA additionally inhibited the resistance of NSCLC xenograft tumors to DDP treatment in vivo.ConclusionsSNHG7 can promote malignant behaviors and DDP resistance in NSCLC cells at least partly via the induction of autophagic activity.

Dataset Information

FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.

Publications

FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets