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Long non-coding RNA LEISA promotes progression of lung adenocarcinoma via enhancing interaction between STAT3 and IL-6 promoter

Abstract

Long non-coding RNAs (lncRNAs) are emerging as a new class of regulators for a variety of biological processes and have been suggested to play pivotal roles in cancer development and progression. Our current study found that a lncRNA, designated enhancing IL-6/STAT3 signaling activation (LEISA, ENST00000603468), functioned as an oncogenic lncRNA in lung adenocarcinoma (LAD), a major form of non-small cell lung carcinoma, which is one of the most frequently diagnosed malignancies with high morbidity and mortality worldwide, and was involved in the regulation of STAT3 induced IL-6 transcription. Our data showed that LEISA was highly expressed in, and correlated with the clinical progression and prognosis of LAD. Ectopic expression of LEISA promoted the proliferation and suppressed apoptosis of LAD cells in vitro and in vivo. Mechanistically, we demonstrated that LEISA recruited STAT3 to bind the promoter of IL-6 and upregulated IL-6 expression. Taken together, our work identifies LEISA as a potential diagnostic biomarker and therapeutic target for LAD.

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Fig. 1: LEISA expression is upregulated in LAD and correlates with poor prognosis.
Fig. 2: LEISA enhances proliferation and suppresses apoptosis of LAD cells in vitro.
Fig. 3: LEISA promotes LAD tumor growth in vivo.
Fig. 4: LEISA upregulates IL-6 expression and activates JAK2/STAT3 signaling.
Fig. 5: LEISA enhances the interaction between STAT3 and IL-6 promoter.
Fig. 6: LEISA expression positively correlates with activation of IL-6/JAK2/STAT3 signaling in LAD.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2017YFA0106300) and the National Natural Science Foundation of China (81972170, 81820108025, 81621004, 81672296, 81922050, 81772473, 81802274); the Science and Technology Program of Guangzhou City (201803010039); the Guangdong MEPP Fund (NO. GDOE [2019]A21); the Natural Science Foundation of Guangdong Province (2019A1515011174); the Fundamental Research Funds for the Central Universities (19ykpy162).

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Wu, S., Liu, B., Zhang, Y. et al. Long non-coding RNA LEISA promotes progression of lung adenocarcinoma via enhancing interaction between STAT3 and IL-6 promoter. Oncogene (2021). https://doi.org/10.1038/s41388-021-01769-7

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