Long non-coding RNAs (lncRNAs) have traditionally been regarded as non-protein-coding transcripts. However, accumulating evidence demonstrates that many lncRNAs contain small open reading frames (sORFs) that are actively translated into functional micropeptides. In cancer, these lncRNA-derived micropeptides regulate diverse hallmarks, including cell proliferation and apoptosis, metabolic reprogramming, metastasis, angiogenesis, and immune evasion. Mechanistically, they modulate enzymatic activity, protein complex assembly, RNA stability, splicing programs, and the subcellular localization of interacting partners. Notably, parental lncRNAs and their encoded micropeptides can exert concordant or divergent biological effects on tumor progression through distinct molecular pathways, highlighting the need to validate the functions of the RNA transcript and the translated peptide independently. Despite recent advances, distinguishing truly functional micropeptides from widespread but nonfunctional translation products and separating RNA-mediated from peptide-mediated effects remain major challenges. Emerging clinical evidence further suggests that lncRNA-derived micropeptides hold promise as diagnostic and prognostic biomarkers. In this review, we systematically explore the functional roles and molecular mechanisms of lncRNA-derived micropeptides across major cancer hallmarks, compare the concordant and divergent biological outcomes of parental lncRNAs and their encoded micropeptides, and discuss their clinical potential as biomarkers and therapeutic targets alongside the current limitations that must be addressed for translational application.
House dust mite (HDM) is a major environmental allergen that promotes cutaneous inflammation and disrupts epidermal barrier-associated processes. Early growth response 1 (EGR1) is an inducible transcription factor implicated in inflammatory skin responses; however, its relationship with epidermal barrier-associated lipid metabolism during allergen exposure remains poorly understood. This study investigated whether Egr1 deficiency is associated with preservation of epidermal barrier-related features and restoration of lipid metabolic transcriptional programs following HDM exposure. Epidermal alterations and filaggrin (FLG) expression were evaluated in wild-type (WT) and Egr1-knockout (KO) mice following topical HDM exposure. A previously generated RNA-seq dataset from WT and Egr1-KO skin with or without HDM treatment was reanalyzed as an exploratory transcriptomic dataset. Expression-change profiling, functional enrichment, and gene set enrichment analyses were used to identify HDM-responsive transcriptional patterns associated with Egr1 deficiency. Selected lipid metabolism-associated genes were independently examined by quantitative real-time PCR. HDM exposure induced epidermal abnormalities and markedly reduced FLG expression in WT mice, whereas these changes were attenuated in Egr1-KO mice. Exploratory transcriptomic profiling suggested that Egr1 deficiency reprogrammed, rather than globally suppressed, the transcriptional response to HDM. Genes suppressed by HDM but restored in Egr1-deficient skin were preferentially associated with lipid metabolic processes, including fatty acid and sphingolipid metabolism. Gene set enrichment analysis further showed reciprocal enrichment of several lipid-related pathways between WT-HDM versus WT-control and KO-HDM versus WT-HDM comparisons. Independent expression analysis supported the recovery of Elovl6, Hacd2, and Cidec in HDM-treated Egr1-KO skin. Egr1 deficiency is associated with attenuation of HDM-induced FLG loss and restoration of selected epidermal lipid metabolism-associated transcriptional patterns. These findings suggest that EGR1-associated inflammatory responses may intersect with epidermal lipid metabolism during allergen exposure and provide a basis for further investigation of EGR1 in the inflammation–barrier interface.
NAC (NAM, ATAF1/2, CUC2) transcription factors are plant-specific regulators of development and abiotic-stress adaptation, yet their properties and functions in the alpine cucurbit Herpetospermum pedunculosum remains unknown. This study aims to conduct a genome-wide identification and characterization of the NAC transcription factor family in H. pedunculosum and to preliminarily explore its potential functions in response to salt stress. NAC genes in the H. pedunculosum genome were identified, followed by analyses of their chromosomal distribution, phylogenetic relationships, gene structures, conserved motifs, and promoter cis-elements, and Gene Ontology (GO) annotation. Their expression patterns were analyzed using transcriptome data from salt stress conditions, and eight salt-responsive genes were validated by RT-qPCR. Finally, the subcellular localization of a representative candidate gene, HpNAC33, was determined experimentally. A total of 80 HpNAC genes were identified, distributed unevenly across 10 chromosomes, and classified them into 16 subfamilies based on phylogenetic analysis. The promoter analyses revealed extensive cis‑regulatory diversity associated with light signaling, development, phytohormone pathways, and stress responses. GO annotation indicated enrichment in terms related to transcription regulator activity, binding, and response to stimulus. Eight salt-responsive genes were selected for RT-qPCR validation, which confirmed their differential expression under salinity. Subcellular localization assays confirmed that HpNAC33 localizes to the nucleus; however, yeast-based transcriptional activation assay did not detect intrinsic transactivation activity for HpNAC33. This study provides a comprehensive genome-wide NAC resource for H. pedunculosum and prioritizes candidate regulators for future dissection of salinity-tolerance mechanisms, while also offering initial insights into the potential mode of action of HpNAC33.
Accurate identification of Channa species and distinction between native and cultured stocks are important for both aquaculture and conservation in Bangladesh. This study combined landmark-based truss morphometrics with mitochondrial cytochrome c oxidase subunit I (COI) barcoding to examine morphological and mitochondrial differentiation among selected Channa species, with particular attention to native Bangladeshi and Vietnam-originated cultured C. striata. Morphometric variation was assessed using 13 homologous landmarks and 26 truss measurements after allometric size standardization, followed by principal component analysis, multivariate analysis of variance, and UPGMA clustering. COI sequences from 21 specimens were analysed together with reference sequences using genetic-distance, substitution-pattern, maximum-likelihood, and maximum-parsimony approaches. The morphometric analyses revealed clear body-shape differences among the examined taxa and between the two C. striata populations. The COI data also separated the major species groups and consistently distinguished native Bangladeshi from Vietnam-originated cultured C. striata. The representative genetic distance between the two C. striata populations was 0.0341, while within-group distances were 0.0441 for the native population and 0.0005 for the cultured stock. Maximum-likelihood and maximum-parsimony trees were generally consistent at the species and population levels, although deeper relationships were less stable and received weaker support. Morphological and molecular clustering were therefore not fully congruent, likely because body shape can be influenced by environmental conditions and phenotypic plasticity, whereas COI reflects maternal lineage history. Overall, the findings support clear morphological and mitochondrial differentiation among the examined Channa taxa and between the two C. striata populations. Broader geographic sampling and the inclusion of nuclear or genome-wide markers will be needed to assess admixture, local adaptation, and population structure more fully.
Drosophila ventral nervous system defective (vnd/NK2.2) encodes a homeodomain (HD) transcription factor essential for establishing neuroblast (NB) identity in the ventral nerve cord. However, its direct downstream targets during embryonic neurogenesis remain largely unknown. This study aimed to identify target genes directly regulated by Vnd and elucidate the molecular mechanisms underlying their regulation during the formation of embryonic NBs. Expression profiles and embryonic phenotypes were analyzed in either vnd6/Y or dpn1/dpn1 single mutants and vnd6/Y; dpn1/dpn1 double mutants using immunofluorescence. Direct binding of the Vnd HD to the deadpan (dpn) promoter was assessed via EMSA, and functional binding sites were validated using dual-luciferase reporter assays in S2 cells. The dosage-dependent relationship between vnd and dpn was characterized in primary neural cultures using real-time PCR and quantitative immunofluorescence. Both vnd6/Y and dpn1/dpn1 single mutants exhibited similar developmental defects, including NB mis-specification and central/peripheral nervous system disorganization. Consistently, vnd6/Y; dpn1/dpn1 double mutants displayed severely aggravated, overlapping neurogenic phenotypes, suggesting their functional convergence in a combinatorial regulatory mechanism. EMSA and reporter assays demonstrated that Vnd HD specifically binds to the distal V2 site (− 810 to − 803 bp from the dpn transcription start site) containing a 5′-AAGT-3′ core motif. In primary cultures, vnd overexpression significantly elevated dpn transcripts and signal intensities, whereas vnd knockdown markedly reduced dpn expression. Our findings demonstrate that Vnd directly binds to a specific cis-regulatory motif within the dpn promoter, functioning as a transcriptional activator to maintain NB identity and architectural integrity during Drosophila embryogenesis.
