A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer

Abstract

AbstracttRNA-derived fragments (tRFs) are a class of small RNAs that occur when tRNAs are broken down by enzymes due to stress. Increasing reports have shown that tRFs are associated with multiple physiological and pathological processes, especially in cancers; however, very little is known of the effects and mechanisms of tRFs. Therefore, further investigation on the biological roles and clinical value of tRFs is required. In this study, we utilized whole-transcriptome sequencing to profile tRFs expression in the tissues and plasma exosomes of patients with colorectal cancer (CRC). Three tRFs (tRF-3022b, tRF-3030b and tRF-5008b) showed an increasing trend in CRC tissues compared to adjacent normal tissues. They also tended to be elevated in plasma exosomes of CRC patients compared to healthy controls. These results indicated that they may be upregulated in cancer cells and then secreted by exosomes. The knockdown of tRF-regulated factors such as AlkB homolog 3 (ALKBH3), tRNA aspartic acid methyltransferase 1 (DNMT2), angiogenin (ANG), and argonaute RISC catalytic component 2 (AGO2) could affect the expression of tRFs. Notably, we found that the decrease in the three tRFs arrests the progression of the CRC cell cycle and induces cell apoptosis. Silencing tRF-3022b could facilitate M2 macrophage polarization. Mechanistically, we found that tRF-3022b binds to galectin 1 (LGALS1) and macrophage migration inhibitory factor (MIF) in CRC cells and reduces polarization by regulating MIF in M2 macrophages. In conclusion, our study revealed the expression pattern of tRFs in both tissue and plasma exosomes and identified a novel tRF, tRF-3022b, which may affect CRC tumor growth and M2 macrophage polarization by binding to LGALS1 and MIF.

Human circulating small non-coding RNA signature as a non-invasive biomarker in clinical diagnosis of acute myeloid leukaemia

“…Due to their broad range of functions in post-translational regulation and the haematopoietic microenvironment, sncRNAs, especially miRNAs, play major roles in maintaining haematopoietic stem cell homeostasis and are well-documented in leukaemia progression, metastasis, and drug resistance [46][47][48][49]. Many studies over the past decades have identified non-canonical sncRNAs such as tsRNAs, rsRNAs, and ysRNAs and revealed their versatile roles in cell homeostasis and disease [35,[50][51][52][53][54][55]. To our knowledge, this study is the first to comprehensively characterize the sncRNA profiles of human blood serum and bone marrow supernatant from people with and without AML, revealing a specific sncRNA profile in AML.…”

Exploring the functional role of tRF-39-8HM2OSRNLNKSEKH9 in hepatocellular carcinoma

“…As one of the most abundant small RNA entities, tRNAs and their derivatives, which take part in the pathogenic process of cancer, have attracted broad attention [ 26 ]. An increasing number of studies have reported that tsRNAs contribute to the occurrence and development of diverse cancers such as pancreatic cancer [ 14 ], breast cancer [ 27 ], non-small cell lung cancer [ 28 ], and colorectal cancer [ 29 ], etc. In addition, many studies have indicated that serum tsRNA could serve as a novel biomarker for the diagnosis of HCC.…”

M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages

“…Recently, Ren et al found that Schwann cell-derived exosomal MFG-E8 modified macrophage/microglial M2 polarization for attenuating inflammation in spinal cord injury [ 48 ]. Lu et al found that a novel tRNA-derived fragment tRF-3022b modulates M2 macrophage polarization contribute to colorectal cancer progression [ 49 ]. Liu et al found that hepatocyte-derived exosomal miR-192–5p plays a critical role in the activation of M1 macrophages polarization and disease progression of nonalcoholic fatty liver disease (NAFLD) [ 50 ].…”