Expression of Mitochondrial Long Non-Coding RNAs, MDL1 and MDL1AS, Are Good Prognostic and/or Diagnostic Biomarkers for Several Cancers, Including Colorectal Cancer

Simple Summary Personalized cancer medicine is based on the right classification of patients that can, then, be treated according to their specific characteristics. This is accomplished by the use of biological markers, so the identification of reliable biomarkers is a primary goal of clinical research. Here, we present two RNA molecules (named MDL1 and MDL1AS) that are generated in the mitochondria and have been heretofore neglected due to a glitch in the official human genome. Both molecules are good prognostic biomarkers in rectal cancer, meaning that their expression can predict which patients will survive more than 5 years after treatment. In addition, MDL1AS is also a good diagnostic biomarker (can distinguish people with/without the disease) for diverse cancers, including those of the colon, rectum, breast, and larynx. Experiments in cancer cells in culture show that these RNAs regulate several hallmarks of cancer, such as mitochondrial function, cell growth, and migration.Abstract 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. 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. 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 reliable prognostic biomarkers of LARC, and MDL1AS expression provides relevant information on the diagnosis of different cancers.