Expression of mitochondrial long non-coding RNAs, MDL1 and MDL1AS, are good prognostic biomarkers for locally advanced rectal cancer (LARC) and MDL1AS is a diagnostic biomarker for LARC and other cancers
Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases of rectal, colon, breast and laryngeal cancers. In addition, a cohort of 69 locally advanced rectal cancer (LARC) patients with a follow-up of more than 5 years was used to determine the prognostic value of these markers. Furthermore, cell lines of colorectal (HCT116) and breast (MDA-MB-231) carcinoma were employed to study the effects of downregulating MDL1AS in vitro. Expression of MDL1AS (but not MDL1) was significantly different in tumor cells than in the surrounding tissue in a tumor type-specific context: in rectal and colon cancer, it was significantly lower in the tumor whereas in breast and laryngeal cancers it was higher in tumor cells. Both MDL1 and MDL1AS were accurate biomarkers for the 5-year survival of LARC patients (p=0.040 and p=0.007, respectively) with promising areas under the curve in the ROC analyses (0.820 and 0.930, respectively). MDL1AS downregulation reduced mitochondrial respiration in both cell lines. Furthermore, this downregulation produced a decrease in growth and migration on colorectal cells but the reverse effects on breast cancer cells. In summary, MDL1 and MDL1AS can be used as efficient prognostic biomarkers of LARC and MDL1AS expression provides relevant information on the diagnosis of different cancers. The physiological effects of these lncRNAs in the cell are complex and tissue type-dependent, and merit further investigation.