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LINC00671 suppresses cell proliferation and metastasis in pancreatic cancer by inhibiting AKT and ERK signaling pathway

Cancer Gene Therapy volume 28, pages 221–233 (2021)Cite this article

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Abstract

Long noncoding RNAs (lncRNAs) represent an emerging field of tumor biology, playing essential roles in cancer cell proliferation, invasion, and metastasis. However, the overall functional and clinical significance of most lncRNAs in pancreatic cancer is not thoroughly understood. Here, we described most of the lncRNAs with aberrant expression patterns in pancreatic cancer as detected by microarray. Quantitative real-time polymerase chain reaction further verified that the expression of LINC00671 was decreased in pancreatic cancer cell lines and patient samples. Furthermore, lower LINC00671 expression was associated with reduced tumor differentiation, aggressiveness, and poor prognosis. Functionally, LINC00671 overexpression inhibited pancreatic cancer cell proliferation, invasion, and migration in vitro, and reduced tumor growth in vivo. LINC00671 is mainly located in the cytoplasm. RNA sequencing and bioinformatics analyses indicated that LINC00671 binds to multiple miRNAs and therefore could be involved in multiple tumor-associated pathways, such as the AMPK signaling pathway and PI3K-Akt signaling pathway. Western blotting and immunohistochemistry further confirmed that LINC00671 overexpression suppressed the AKT, ERK, and epithelial-mesenchymal transition pathways. Overall, these results indicated that LINC00671 acts as a novel tumor suppressor in pancreatic cancer. Our findings may provide a new potential target for the treatment of pancreatic cancer.

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Fig. 1: Transcriptomic landscape of pancreatic cancer.
Fig. 2: The general overview of LINC00671 in the database.
Fig. 3: LINC00671 was downregulated in pancreatic cancer and associated with poor prognosis.
Fig. 4: Overexpression of LINC00671 inhibited pancreatic cancer cell proliferation, colony formation, migration, and invasion.
Fig. 5: Overexpression of LINC00671 inhibited tumor growth of pancreatic cancer xenografts in vivo.
Fig. 6: The cellular localization, distribution, and ceRNA network of LINC00671.
Fig. 7: Overexpression of LINC00671 suppressed pancreatic cancer development by regulating EMT, AKT, and ERK pathways.

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Acknowledgements

The authors thank Kun Liu and Huimin Wang (Department of Hepatobiliary Surgery of Xijing Hospital) for collecting the tissue samples and the follow-up information

Funding

This study was funded by the National Natural Science Foundation of China (grant numbers 81672339, 81874051, and 81900571).

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Author notes

  1. These authors contributed equally: Shibin Qu, Kunwei Niu, Jianlin Wang

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China

    Shibin Qu, Kunwei Niu, Jianlin Wang, Jimin Dai, Zhibin Lin, Xisheng Yang, Xuan Zhang, Zhengcai Liu & Haimin Li

  2. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Anutosh Ganguly & Yuzi Tian

  3. Research Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA

    Anutosh Ganguly

  4. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Science, Bejing Institute of Lifeomics, Beijing, China

    Chao Gao

  5. Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China

    Yuzi Tian

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Qu, S., Niu, K., Wang, J. et al. LINC00671 suppresses cell proliferation and metastasis in pancreatic cancer by inhibiting AKT and ERK signaling pathway. Cancer Gene Ther 28, 221–233 (2021). https://doi.org/10.1038/s41417-020-00213-4

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