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MALAT1-KTN1-EGFR regulatory axis promotes the development of cutaneous squamous cell carcinoma



Long noncoding RNAs (LncRNAs), including MALAT1, are critical regulators of tumor development. However, the roles and molecular mechanisms of LncRNAs in cutaneous squamous cell carcinoma (cSCC) remain underexplored. In this study, functional studies using in vitro cellular and in vivo xenograft models confirmed the pro-carcinogenic roles of MALAT1 in cSCC. Further, MALAT1 was identified to regulate epidermal growth factor receptor (EGFR) protein expression but did not affect EGFR mRNA expression. Transcriptomic sequencing identified kinectin 1 (KTN1) as the key mediator for MALAT1 regulation of EGFR. Mechanistic study revealed that MALAT1 interacts with c-MYC to form a complex and directly binds to the promoter region of KTN1 gene and enhances its transactivation to positively regulate EGFR protein expression. Our findings, therefore, establish a novel c-MYC-assisted MALAT1-KTN1-EGFR axis, which contributes to cSCC development and may serve as novel target for therapeutic intervention.

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The work described in this paper was substantially supported by grants from the National Natural Science Foundation of China (Grant Nos. 81573076, 81172634;; a grant from Guangdong Provincial Department of Science and Technology, China (Grant No. 2016A030313738;, and grants from the School of Public Health of Southern Medical University, China (Grant No. GW201612;

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics statement

This study was approved by the Institutional Review Board of Nanfang Hospital affiliated to Southern Medical University, and all patients provided written informed consent for the use of surgical samples. Mice transportation, housing, and breeding were conducted according to the recommendations of ‘‘The use of non-human primates in research.’’ The mice were killed by cervical dislocation to prevent suffering. The Southern Medical University Animal Care and Use Committee approved all procedures involving the mice.

Correspondence to Liang Zhou or Zhenhua Ding.

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