The long antisense non-coding RNA HOXA transcript at the distal tip (LncRNA HOTTIP) in health and disease: a comprehensive review and in silico analysis.

Since lncRNAs are RNA transcripts with more than 200 nucleotides that do not encode proteins, they are functional units themselves. It has been demonstrated that they participate in a variety of biological processes. One particular long noncoding RNA, known as HOXA transcript at the distal tip (HOTTIP), is encoded from a genomic region in the 5' tip of the HOXA locus. It has been linked to the development and spread of human cancer. A growing body of evidence indicates that dysregulation of HOTTIP is linked to a number of cancers and impacts the prognosis and survival of cancer patients but what are the normal physiological functions of HOTTIP in non-cancerous tissues? And how does the dysregulation of HOTTIP contribute to non-malignant diseases? These are major questions to be answered. In this study, we provide an overview of the current understanding of the significance of lncRNA HOTTIP and, for the first time, describe its participation in normal physiological function. Moreover, what are the most critical knowledge gaps in the current understanding of HOTTIP, and how can these gaps be addressed experimentally? These are other questions we aimed to answer, in addition to providing insight into its function in chemotherapeutic resistance and its usefulness in the diagnosis and prognosis of numerous malignancies. Finally, we also show how mutations in this lncRNA, even in a single nucleotide, affect many diseases' fates including malignancies and other non-malignant ones.