Long non-coding RNA MLLT4 antisense RNA 1 induces autophagy to inhibit tumorigenesis of cervical cancer through modulating the myosin-9/ATG14 axis

• Published in: Scientific reports 2024-03, Vol.14 (1), p.6379-6379, Article 6379
• Main Authors: Zhang, Tingting, Ji, Tiantian, Duan, Zhao, Xue, Yuanyuan
• Format: Article
• Language: English
• Subjects: 631/67; 631/80; Adaptor Proteins, Vesicular Transport; Antisense RNA; Autophagy; Autophagy - genetics; Autophagy-Related Proteins - genetics; Carcinogenesis - genetics; Cell Line, Tumor; Cell migration; Cell Proliferation - genetics; Cell Transformation, Neoplastic - genetics; Cervical cancer; Cytoskeletal Proteins - metabolism; Female; Fluorescence in situ hybridization; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Immunoprecipitation; In Situ Hybridization, Fluorescence; lncRNA; Mass spectrometry; Mass spectroscopy; MicroRNAs - genetics; multidisciplinary; Myosin; Myosins - genetics; Myosins - metabolism; Non-coding RNA; Rapamycin; RNA, Antisense - genetics; RNA, Antisense - metabolism; RNA, Long Noncoding - metabolism; Science; Science (multidisciplinary); Tumor suppressor genes; Tumorigenesis; Uterine Cervical Neoplasms - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-55644-y

The regulatory mechanism of long non-coding RNAs (lncRNAs) in autophagy is as yet not well established. In this research, we show that the long non-coding RNA MLLT4 antisense RNA 1 (lncRNA MLLT4-AS1) is induced by the MTORC inhibitor PP242 and rapamycin in cervical cells. Overexpression of MLLT4-AS1 promotes autophagy and inhibits tumorigenesis and the migration of cervical cancer cells, whereas knockdown of MLLT4-AS1 attenuates PP242-induced autophagy. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between MLLT4-AS1 and other associated targets, such as myosin-9 and autophagy-related 14(ATG14). MLLT4-AS1 was upregulated by H3K27ac modification with PP242 treatment, and knockdown of MLLT4-AS1 reversed autophagy by modulating ATG14 expression. Mechanically, MLLT4-AS1 was associated with the myosin-9 protein, which further promoted the transcription activity of the ATG14 gene. In conclusion, we demonstrated that MLLT4-AS1 acts as a potential tumor suppressor in cervical cancer by inducing autophagy, and H3K27ac modification-induced upregulation of MLLT4-AS1 could cause autophagy by associating with myosin-9 and promoting ATG14 transcription.