m6A-Modified SFTA1P Acts as a Tumor Suppressor in Non–Small Cell Lung Cancer by Regulating TGFBR2 and P-TEFb

SFTA1P is a pseudogene-derived long noncoding RNA and has become a master regulator in tumor carcinogenesis and progression processes. SFTA1P has been reported as a potential diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). The downregulation of SFTA1P in tumor tissue has been associated with poor prognosis; however, the detailed molecular mechanism and biological functions still need to be investigated. We demonstrated that SFTA1P inhibited the growth and metastasis of NSCLC in vitro and in vivo. SFTA1P had dual functions in the cytoplasm and nucleus: In the cytoplasm, SFTA1P can serve as a "sponge" for miR-665 to increase the expression level of TGFBR2; in the nucleus, SFTA1P can bind the positive transcription elongation factor b and subsequently inhibit the transcriptase activity of RNA polymerase II. The regulation of TGFBR2 and positive transcription elongation factor b via SFTA1P depends on its subcellular localization, which was affected by the status of the N6-methyladenosine RNA modification of SFTA1P. Our research demonstrated that the candidate tumor-suppressor SFTA1P is extensively involved in NSCLC, which may offer novel insights into NSCLC oncogenesis. IMPLICATIONS: SFTA1P is downregulated in NSCLC and had dual functions in the cytoplasm and nucleus.