PINTology: A short history of the lncRNA LINC‐PINT in different diseases

Abstract

LINC-PINT is a p53-induced long intergenic noncoding transcript that plays a crucial role in many diseases, especially cancer. This long noncoding RNA (lncRNA) gene produces in total 102 (LNCipedia) alternatively spliced variants (LINC-PINT:1 to LINC-PINT:102). The functions of known variants include RNA transcripts, host transcripts for circular RNA (circRNA) generation and as sources for the translation of short peptides. In most human tumors, LINC-PINT is down-regulated where it serves as a tumor suppressor. However, the diversity of its functions in other maladies signifies its general clinical importance. Current LINC-PINT molecular functions include RNA-protein interactions, miRNA sponging and epigenetic modulation with these mechanisms operating in different cellular contexts to exert effects on biological processes ranging from DNA damage responses, cell cycle and growth arrest, senescence, cell migration and invasion, and apoptosis. Genetic polymorphisms in LINC-PINT have also been functionally associated with cancer and other pathologies including the autoimmune diseases pemphigus foliaceus and arthritis. Hence, LINC-PINT shows great potential as a clinical biomarker, especially for the diagnosis and prognosis of cancer. In this review, we explore the current knowledge highlighting the distinctive molecular functions of LINC-PINT in specific cancers and other disease states.Ihtisham Bukhari and Muhammad Riaz Khan contributed equally to this study.

Clinical implications of lncRNA LINC-PINT in cancer

“…As such, their expression and function are often altered in disease states (Kleinbrink et al, 2021;Yang et al, 2021;Anderson and Anderson, 2022;Dietlein et al, 2022;Erdogan et al, 2022) with selected examples now being used as diagnostic markers for various diseases including cancers (Li et al, 2019;Deng and Zou, 2022;Najafi et al, 2022;Zhang et al, 2022). Among these, one particular lncRNA called LINC-PINT (P53 Induced long Non-coding Transcript) appears exceptional because of its universalized functions and relationship to the famous tumor suppressor gene P53 (He et al, 2021;Bukhari et al, 2022). Indeed, like P53, LINC-PINT was first proposed as an oncogene but later revealed as a tumor suppressor in human cancers.…”

“…LINC-PINT contributes to a variety of biological processes impacting cancer cell growth and metastasis, with involvement in processes ranging from DNA damage responses to cell senescence and apoptosis (Simchovitz et al, 2020;He et al, 2021;Wang et al, 2021;Xiang et al, 2021;Zhang et al, 2021;Bukhari et al, 2022). It has also been shown to be an essential regulator of many other diseases, including autoimmune diseases (Wang and Zhao, 2020;Salviano-Silva et al, 2021).…”

“…It has also been shown to be an essential regulator of many other diseases, including autoimmune diseases (Wang and Zhao, 2020;Salviano-Silva et al, 2021). These functions arise through interactions affecting epigenetic regulation or direct interactions with other biomolecules, including proteins and other lncRNAs (Xu et al, 2019;Bukhari et al, 2022). Some alternatively spliced variants of LINC-PINT also act as host transcripts for circular RNA (circRNA) generation, and these can serve as sources for the translation of short functional peptides (Xiang et al, 2021).…”

“…Some alternatively spliced variants of LINC-PINT also act as host transcripts for circular RNA (circRNA) generation, and these can serve as sources for the translation of short functional peptides (Xiang et al, 2021). More than 100 alternatively spliced variants of LINC-PINT have been identified (Bukhari et al, 2022). Still, to date, only a few of these have been thoroughly studied-a feature earning the name PINTology to describe the current and future studies involving LINC-PINT.…”

LINC-PINT suppresses cisplatin resistance in gastric cancer by inhibiting autophagy activation via epigenetic silencing of ATG5 by EZH2

“…Recent studies have reported that the lncRNA, p53-induced transcript (LINC-PINT) is downregulated in several cancer types, including colon cancer, lung cancer, breast cancer, glioblastoma, and GC ( Marin-Bejar et al, 2013 ; Marin-Bejar et al, 2017 ; He et al, 2021 ; Bukhari et al, 2022 ). LINC-PINT directly interacts with the polycomb repressive complex 2 (PRC2) to regulate the expression of downstream genes ( Marin-Bejar et al, 2013 ; Marin-Bejar et al, 2017 ).…”