Advances of Long Non-Coding RNAs as Potential Biomarkers for Tuberculosis: New Hope for Diagnosis?

Abstract

Tuberculosis (TB), one of the top ten causes of death globally induced by the infection of Mycobacterium tuberculosis (Mtb), remains a grave public health issue worldwide. With almost one-third of the world's population getting infected by Mtb, between 5% and 10% of these infected individuals are predicted to develop active TB disease, which would not only result in severe tissue damage and necrosis, but also pose serious threats to human life. However, the exact molecular mechanisms underlying the pathogenesis and immunology of TB remain unclear, which significantly restricts the effective control of TB epidemics. Despite significant advances in current detection technologies and treatments for TB, there are still no appropriate solutions that are suitable for simultaneous, early, rapid, and accurate screening of TB. Various cellular events can perturb the development and progression of TB, which are always associated with several specific molecular signaling events controlled by dysregulated gene expression patterns. Long non-coding RNAs (lncRNAs), a kind of non-coding RNA (ncRNA) with a transcript of more than 200 nucleotides in length in eukaryotic cells, have been found to regulate the expression of protein-coding genes that are involved in some critical signaling events, such as inflammatory, pathological, and immunological responses. Increasing evidence has claimed that lncRNAs might directly influence the susceptibility to TB, as well as the development and progression of TB. Therefore, lncRNAs have been widely expected to serve as promising molecular biomarkers and therapeutic targets for TB. In this review, we summarized the functions of lncRNAs and their regulatory roles in the development and progression of TB. More importantly, we widely discussed the potential of lncRNAs to act as TB biomarkers, which would offer new possibilities in novel diagnostic strategy exploration and benefit the control of the TB epidemic.

Keywords: biomarker; diagnosis; function; long non-coding RNA; tuberculosis.

Figure 1

Potential roles of lncRNAs in TB. (A) LncRNAs regulate the transcription factors involved in DNA damage, repair, and genome stability. (B) LncRNAs regulate the activity of miRNAs. (C) Regulation of protein translation by lncRNAs. (D) LncRNAs regulate apoptosis and autophagy in macrophages upon Mtb infection. (E) T cells promote host defense by releasing Th1 cytokines to act on Mtb-infected macrophages. (F) A proposed model for the involvement of lncRNAs in adaptive immunity against Mtb. LncRNA-CD244 localizes in the nucleus and mediates the recruitment of the polyoma protein EZH2, which trimethylates H3K27 of the IFN-γ and TNF-α promoters, thereby inducing suppressive chromatin (heterochromatin) at the inf-g and tnf-a motifs [26]. (G) Exosomes mediate intercellular information exchange.