The long noncoding RNA Arrl1 inhibits neurite outgrowth by functioning as a competing endogenous RNA during neuronal regeneration in rats

Abstract

The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Therefore, identifying the key modulators of nerve regeneration may help improve axon regeneration and functional recovery after injury. Unlike for classical transcription factors and regeneration-associated genes, the function of long noncoding RNAs (lncRNAs) in the regulation of neuronal regeneration remains mostly unknown. In this study, we used RNA-Seq–based transcriptome profiling to analyze the expression patterns of lncRNAs and mRNAs in rat dorsal root ganglion (DRG) following sciatic nerve injury. Analyses using the lncRNA-mRNA co-expression network, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway databases indicated that the lncRNA Arrl1 decreases neurite outgrowth after neuronal injury. shRNA-mediated Arrl1 silencing increased axon regeneration both in vitro and in vivo and improved functional recovery of the sciatic nerve. Moreover, inhibiting an identified target gene of Arrl1, cyclin-dependent kinase inhibitor 2B (Cdkn2b), markedly promoted neurite outgrowth of DRG neurons. We also found that Arrl1 acts as a competing endogenous RNA that sponges a Cdkn2b repressor, microRNA-761 (miR-761), and thereby up-regulates Cdkn2b expression during neuron regeneration. We conclude that the lncRNA Arrl1 affects the intrinsic regeneration of DRG neurons by derepressing Cdkn2b expression. Our findings indicate a role for an lncRNA-microRNA-kinase pathway in the regulation of axon regeneration and functional recovery following peripheral nerve injury in rats.

Imbalance of Molecular Module of TINCR-miR-761 Promotes the Metastatic Potential of Early Triple Negative Breast Cancer and Partially Offsets the Anti-Tumor Activity of Luteolin

“…For example, miR-761 can mediate the development of NSCLC through the regulation of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR), 24 participate in the development of thyroid papillary carcinoma through the target control of HOXA11 antisense RNA (HOXA11-AS), 25 and is targeted by Arrl1 to regulate neurite growth during neurite regeneration in rats. 26 However, only the molecular module of TINCR-miR-761 is highly correlated with TNBC, which has been confirmed in our research. Finally, we also studied the influence of TINCR-miR-761 molecular module on the anti-TNBC mechanism of LU.…”

Diazoxide Protects against Myocardial Ischemia/Reperfusion Injury by Moderating ERS via Regulation of the miR-10a/IRE1 Pathway

“…The aberrant miRNA expressions of the myocardial samples were analyzed by miRNA sequencing as previously described [ 26 , 27 ] Briefly, total RNA of the tissues was extracted to prepare the small RNA sequencing library by using the NEBNext Multiplex Small RNA Library Prep Set for Illumina (NEB, USA) according to the manufacturer's instruction. The libraries were finally sequenced, and the Solexa CHASTITY quantity filtered reads were harvested as clean reads.…”

Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

“…Synage is one of the few examples of predominantly cytosolic lncRNAs, and it has been suggested to have an additional function as organizer of the synaptic scaffold [ 131 ]. Among other examples of lncRNAs acting in a similar manner, it is worth mentioning Arrl1 , which acts as a sponge of miR-761 that would decrease the levels of Cdkn2b and thus inhibit neurite outgrowth after neuronal injury [ 132 ].…”