LINC00622 transcriptionally promotes RRAGD to repress mTORC1-modulated autophagic cell death by associating with BTF3 in cutaneous melanoma.

Autophagy plays critical and complicated roles in tumors. As the central hub of nutrient signaling and cell growth, mTOR constitutes mTORC1 to be the main gateway for modulating autophagy. Yet, the regulatory mechanisms of mTORC1-regulated autophagy in tumors are not fully deciphered. Here, we report a novel long noncoding RNA, LINC00622, which modulates mTORC1-regulated autophagy in cutaneous melanoma. Functionally, LINC00622 acts as a pro-oncogenic factor to promote proliferation, colony formation, migration and invasion in melanoma while suppressing cell death. Mechanistically, LINC00622 associates with and recruits BTF3 to transcriptionally enhance RRAGD expression for activating mTORC1 and thus inhibiting autophagic cell death, which contributes to the development of cutaneous melanoma. Our findings not only demonstrated the oncogenic role of LINC00622 via RRAGD/mTORC1 axis to repress autophagic cell death in cutaneous melanoma, but also offer novel treatment targets for melanoma therapy.