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LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway

Cancer Gene Therapy volume 29, pages 1285–1295 (2022)Cite this article

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Abstract

Lung squamous cell carcinoma (LUSC) represents one of the commonest types of lung cancer featured with high morbidity and poor prognosis. Many types of research have documented that long noncoding RNAs (lncRNAs) exert crucial functions in the development of cancers, and LUSC is included. In our study, we aimed at unveiling the mechanism underlying long intergenic nonprotein coding RNA 0649 (LINC00649) in LUSC cells. As a result, LINC00649 was discovered to be with high expression in LUSC cells. Moreover, it was confirmed through functional assays that the knockdown of LINC00649 hindered the occurrence and progression of LUSC. Results of mechanism assays validated that E2F transcription factor 7 (E2F7) was a transcription activator of LINC00649 and induced its up-regulation in LUSC cells. Furthermore, LINC00649 recruited TAF15, which is TATA-box binding protein associated factor 15 to stabilize mitogen-activated protein kinase 6 (MAPK6) expression and activate the transcription of MAPK6, thereby enhancing MAPK6 expression to activate the MAPK signaling pathway. Eventually, results of rescue assays suggested that overexpression of MAPK6 offset the influence of LINC00649 silencing on LUSC progression. In summary, our research determined the E2F7/LINC00649/TAF15/MAPK6/MAPK signaling pathway in regulating LUSC development, which made LINC00649 a potential biomarker for LUSC treatment.

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Fig. 1: Knockdown of LINC00649 hinders cell proliferation and accelerates cell apoptosis in LUSC.
Fig. 2: LINC00649 contributes to the development of LUSC.
Fig. 3: Transcription factor E2F7 induces the upregulation of LINC00649.
Fig. 4: LINC00649 recruits TAF15 protein.
Fig. 5: LINC00649 and TAF15 activate MAPK signaling pathway.
Fig. 6: TAF15 stabilizes MAPK6 expression and activates the transcription of MAPK6.
Fig. 7: Overexpression of MAPK6 reverses the inhibitory role of LINC00649 knockdown in the development of LUSC.

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Acknowledgements

We are grateful for the help from all lab personnel in this research.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, 250100, Shandong, China

    Huaiyang Zhu & Qing Wang

  2. Department of Cardio-Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, 250100, Shandong, China

    Qingyuan Liu

  3. Department of General Surgery, Shandong Provincial Chest Hospital, Jinan, 250100, Shandong, China

    Xiaobo Yang

  4. Department of Respiratory Medicine, Shandong Provincial Chest Hospital, Jinan, 250100, Shandong, China

    Caihong Ding & Yu Xiong

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  1. Huaiyang Zhu
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Correspondence to Yu Xiong.

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Zhu, H., Liu, Q., Yang, X. et al. LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway. Cancer Gene Ther 29, 1285–1295 (2022). https://doi.org/10.1038/s41417-021-00410-9

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