Comprehensive analyses of molecular features, prognostic values, and regulatory functionalities of m6A-modified long non-coding RNAs in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) has a high incidence and recurrence rate. N6-methyladenosine (m⁶A) modification of RNA has become a promising epigenetic marker in tumors. The dysregulation of both RNA m⁶A levels and m⁶A regulator expression levels reportedly affects essential biological processes in various tumors. Long non-coding RNAs (lncRNAs), a subgroup of RNAs over 200 nucleotides in length that do not code for protein, can be modified and regulated by m⁶A, but the relevant profile in LUAD remains unclear.

Results: The m⁶A levels of total RNA were decreased in LUAD tumor tissues and cells. Multiple m⁶A regulators were abnormally expressed at both the RNA and protein levels, and were related in expression patterns and functionally synergistic. Our microarray revealed 2846 m⁶A-modified lncRNA transcripts as well as its molecular features, 143 of which were differentially m⁶A-modified and manifested a negative correlation between expression levels and m⁶A modification levels. More than half of the differentially m⁶A-modified lncRNAs associated with dysregulated expression. The 6-MRlncRNA risk signature was a reliable indicator for assessing survival time of LUAD patients. The competitive endogenous regulatory network suggested a potential m⁶A-induced pathogenicity in LUAD.

Conclusions: These data have demonstrated that differential RNA m⁶A modification and m⁶A regulator expression levels were identified in LUAD patients. In addition, this study provides evidence increasing the understanding of molecular features, prognostic values, and regulatory functionalities of m⁶A-modified lncRNAs in LUAD.