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LncRNA KTN1-AS1 promotes the progression of non-small cell lung cancer via sponging of miR-130a-5p and activation of PDPK1

Oncogene volume 39, pages 6157–6171 (2020)Cite this article

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Abstract

Non-small cell lung cancer (NSCLC) is the major cause of cancer-associated death worldwide, but its underlying mechanisms remain to be fully elucidated. Long noncoding RNAs (lncRNAs) are known to play an important role in the aberrant regulation of gene expression in many cancers, including NSCLC. Here, we investigated the involvement of the lncRNA KTN1-AS1 in NSCLC. We found that KTN1-AS1 expression was upregulated in NSCLC tissue and was positively associated with poor prognosis. KTN1-AS1 knockdown inhibited cell growth and proliferation, increased apoptosis, and modulated the expression of cell cycle- and apoptosis-related proteins (cyclin A1, cyclin-dependent kinase 2, Bcl2, and Bax) in NSCLC cell lines and tumour xenografts in nude mice. KTN1-AS1 bound to and directly regulated the expression of miR-130a-5p. Notably, miR-130a-5p overexpression suppressed NSCLC cell proliferation and increased apoptosis in vitro and in vivo, and this effect was reversed by KTN1-AS1 overexpression. Finally, we showed that KTN1-AS1 modulated the expression of 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a miR-130a-5p target and key regulator of autophagy in NSCLC cells. Taken together, our results suggest that the KTN1-AS1/miR-130a-5p/PDPK1 pathway may be a potential therapeutic target for NSCLC.

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Fig. 1: KTN1-AS1 expression is upregulated in NSCLC tissues and is associated with poor prognosis.
Fig. 2: Knockdown of KTN1-AS1 suppresses NSCLC cell proliferation and increases apoptosis in vitro.
Fig. 3: Knockdown of KTN1-AS1 suppresses NSCLC tumour growth in vivo.
Fig. 4: KTN1-AS1 and miR-130a-5p are reciprocally regulated in NSCLC cells.
Fig. 5: miR-130a-5p overexpression attenuates the oncogenic activity of KTN1-AS1.
Fig. 6: Overexpression of miR-130a-5p suppresses NSCLC tumour growth in vivo.
Fig. 7: PDPK1 mRNA is a miR-130a-5p target and is cooperatively regulated by miR-130a-5p and KTN1-AS1.
Fig. 8: Knockdown of PDPK1 abolishes the effects of anti-miR-130a-5p in NSCLC cells in vitro.
Fig. 9: KTN1-AS1, miR-130a-5p, and PDPK1 signalling regulates autophagy in NSCLC cells.

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Acknowledgements

We thank Anne M. O’Rourke, Ph.D., from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript. The results shown here are in whole or part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Funding

This work was supported by the National Natural Science Foundation of China (81602636), General Program of Jiangsu Cancer Hospital (ZM201809), Jiangsu Provincial Medical Youth Talent (QNRC2016645), Young Talents Program of Jiangsu Cancer Hospital(QL201814), Nanjing Medical Science and Technology Development Project (ZKX15049), Key Project of Science of Sichuan Education Department (18ZA0164) and Natural Science Foundation of Chengdu Medical College (CYZ18-04).

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  1. These authors contributed equally: Chenchen Li, Wei Zhao, Xuan Pan

Authors and Affiliations

  1. Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital& Jiangsu Institute of Cancer Research, Nanjing, People’s Republic of China

    Chenchen Li, Xuan Pan, Xiaoyou Li, Fei Yan, Siwen Liu, Jifeng Feng & Jianwei Lu

  2. School of Laboratory Medicine/Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, People’s Republic of China

    Wei Zhao

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Li, C., Zhao, W., Pan, X. et al. LncRNA KTN1-AS1 promotes the progression of non-small cell lung cancer via sponging of miR-130a-5p and activation of PDPK1. Oncogene 39, 6157–6171 (2020). https://doi.org/10.1038/s41388-020-01427-4

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