ARAP1-AS1: a novel long non-coding RNA with a vital regulatory role in human cancer development.

Long non-coding RNAs (lncRNAs) have garnered significant attention in biomedical research due to their pivotal roles in gene expression regulation and their association with various human diseases. Among these lncRNAs, ArfGAP With RhoGAP Domain, Ankyrin Repeat, And PH Domain 1 - Antisense RNA 1 (ARAP1-AS1) has recently emerged as an novel oncogenic player. ARAP1-AS1 is prominently overexpressed in numerous solid tumors and wields influence by modulating gene expression and signaling pathways. This regulatory impact is realized through dual mechanisms, involving both competitive interactions with microRNAs and direct protein binding. ARAP1-AS1 assumes an important role in driving tumorigenesis and malignant tumor progression, affecting biological characteristics such as tumor expansion and metastasis. This paper provides a concise review of the regulatory role of ARAP1-AS1 in malignant tumors and discuss its potential clinical applications as a biomarker and therapeutic target. We also address existing knowledge gaps and suggest avenues for future research. ARAP1-AS1 serves as a prototypical example within the burgeoning field of lncRNA studies, offering insights into the broader landscape of non-coding RNA molecules. This investigation enhances our comprehension of the complex mechanisms that govern the progression of cancer.

LncRNA-MUF: A Novel Oncogenic Star with Potential as a Biological Marker and Therapeutic Target for Gastrointestinal Malignancies.

Gastrointestinal (GI) cancers pose a significant global health challenge, characterized by a high incidence and poor prognosis. The delayed detection and occurrence of metastasis contribute to the overall low survival rates associated with these cancers. Therefore, there is an urgent need to identify novel molecular targets for effective GI cancer treatment. Recent research has shed light on the potential of long non-coding RNAs (lncRNAs) as promising targets in cancer therapy, given their strong association with carcinogenesis and profound impact on tumor development. Among these lncRNAs, lncRNA-MUF, also known as LINC00941, has emerged as a key player in oncogenic regulation, specifically implicated in the progression of various GI cancers, including esophageal, gastric, colorectal, hepatic, and pancreatic cancer. This review aims to provide an updated and focused analysis of the regulatory roles of LINC00941 in the initiation and progression of GI cancer. Our objective is to unravel the underlying molecular mechanisms through which LINC00941 influences GI cancer phenotypes both in vivo and in vitro, with a special emphasis on the key molecules and signaling pathways involved. Additionally, LINC00941 has demonstrated clinical significance in terms of clinical pathology, prognosis, and diagnosis in GI tumors, further reinforcing its potential as a novel therapeutic target.

Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma.

Background: Previous studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC). Methods: Based on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments. Results: This study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration. Conclusion: PANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.

Heterozygous frameshift mutation in FaMYB10 is responsible for the natural formation of red and white-fleshed strawberry (Fragaria x ananassa Duch).

During natural evolution and artificial selection, the fruit color of many species has been repeatedly gained or lost and is generally associated with mutations in genes encoding R2R3-MYB transcription factors, especially MYB10. In this study, we show that a heterozygous frameshift mutation (FaMYB10AG-insert/FaMYB10wild ) is responsible for the loss of anthocyanins in the flesh of cultivated strawberry. Comparative transcriptomic and metabolomic analyses of red- and white-fleshed strawberry indicated that the low expression level of FaUFGT (flavonol-O-glucosyltransferases) was responsible for the loss of anthocyanins and accumulation of proanthocyanidin in the white-fleshed strawberry and was the crucial gene that encodes enzymes of the anthocyanin biosynthesis pathway. Accordingly, overexpression and silencing of FaUFGT altered anthocyanin content and changed the flesh color of strawberry fruits. Furthermore, whole-genome resequencing analyses identified an AG insertion in the FaMYB10 coding region (FaMYB10AG-insert ) of white-fleshed strawberry. Y1H and EMSA assays showed that FaMYB10wild was able to bind to the promoter of the FaUFGT gene, while the FaMYB10AG-insert could not. The skin and flesh color were tightly linked to the number of fully functional FaMYB10 copies in the selfing progeny of white-fleshed strawberry. Our results suggested that heterozygous frameshift mutation of FaMYB10 resulted in the loss of the ability to activate the expression of the FaUFGT gene, was responsible for the natural formation of red and white-fleshed strawberry.

The complexity of the Fragaria x ananassa (octoploid) transcriptome by single-molecule long-read sequencing.

Strawberry (Fragaria x ananassa) is an allopolyploid species with diverse and complex transcripts. The regulatory mechanisms of fruit development and maturation have been extensively studied; however, little is known about the signaling mechanisms that direct this process in octoploid strawberry (Fragaria x ananassa). Here, we used long-read sequencing (LRS) technology and RNA-seq analysis to investigate the diversity and complexity of the polyploid transcriptome and differentially expressed transcripts along four successive fruit developmental stages of cultivated strawberry. We obtained a reference transcriptome with 119,897 unique full-length isoforms, including 2017 new isoforms and 2510 long noncoding RNAs. Based on the genome of the plausible progenitor (Fragaria vesca), 20,229 alternative splicing (AS) events were identified. Using this transcriptome, we found 17,485 differentially expressed transcripts during strawberry fruit development, including 527 transcription factors (TFs) belonging to 41 families. The expression profiles of all members of the auxin, ABA pathway, and anthocyanin biosynthesis gene families were also examined, and many of them were highly expressed at the ripe fruit stage, strongly indicating that the role of those genes is in the regulation of fruit ripening. We produce a high-quality reference transcriptome for octoploid strawberry, including much of the full-length transcript diversity, to help understand the regulatory mechanisms of fruit development and maturation of polyploid species, particularly via elucidation of the biochemical pathways involved in auxin, ABA, and anthocyanin biosynthesis.

Erratum: Author Correction: The complexity of the Fragaria x ananassa(octoploid) transcriptome by single-molecule long-read sequencing.

[This corrects the article DOI: 10.1038/s41438-019-0126-6.].

[Genome-wide identification and expression analysis of auxin-related gene families in grape].

The auxin response gene family adjusts the auxin balance and the growth hormone signaling pathways in plants. Using bioinformatics methods, the auxin-response genes from the grape genome database are identified and their chromosomal location, gene collinearity and phylogenetic analysis are performed. Probable genes include 25 AUX_IAA, 19 ARF, 9 GH3 and 42 LBD genes, which are unevenly distributed on all 19 chromosomes and some of them formed distinct tandem duplicate gene clusters. The available grape microarray databases show that all of the auxin-response genes are expressed in fruit and leaf buds, and significant overexpressed during fruit color-changing, bud break and bud dormancy periods. This paper provides a resource for functional studies of auxin-response genes in grape leaf and fruit development.

A role for PacMYBA in ABA-regulated anthocyanin biosynthesis in red-colored sweet cherry cv. Hong Deng (Prunus avium L.).

The MYB transcription factors and plant hormone ABA have been suggested to play a role in fruit anthocyanin biosynthesis, but supporting genetic evidence has been lacking in sweet cherry. The present study describes the first functional characterization of an R2R3-MYB transcription factor, PacMYBA, from red-colored sweet cherry cv. Hong Deng (Prunus avium L.). Transient promoter assays demonstrated that PacMYBA physically interacted with several anthocyanin-related basic helix-loop-helix (bHLH) transcription factors to activate the promoters of PacDFR, PacANS and PacUFGT, which are thought to be involved in anthocyanin biosynthesis. Furthermore, the immature seeds of transgenic Arabidopsis plants overexpressing PacMYBA exhibited ectopic pigmentation. Silencing of PacMYBA, using a Tobacco rattle virus (TRV)-induced gene silencing technique, resulted in sweet cherry fruit that lacked red pigment. ABA treatment significantly induced anthocyanin accumulation, while treatment with the ABA biosynthesis inhibitor nordihydroguaiaretic acid (NDGA) blocked anthocyanin production. PacMYBA expression peaked after 2 h of pre-incubation in ABA and was 15.2-fold higher than that of sweet cherries treated with NDGA. The colorless phenotype was also observed in the fruits silenced in PacNCED1, which encodes a key enzyme in the ABA biosynthesis pathway. The endogenous ABA content as well as the transcript levels of six structural genes and PacMYBA in PacNCED1-RNAi (RNA interference) fruit were significantly lower than in the TRV vector control fruit. These results suggest that PacMYBA plays an important role in ABA-regulated anthocyanin biosynthesis and ABA is a signal molecule that promotes red-colored sweet cherry fruit accumulating anthocyanin.

Identification and characterization of FaSOC1, a homolog of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 from strawberry.

A MADS-box gene SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) integrates multiple flowering signals to regulate floral transition in Arabidopsis. Strawberry (Fragaria spp.) is an economically important fruit crop, but its molecular control of flowering is largely unknown. In this study, a SOC1-like gene, FaSOC1, was isolated and characterized from strawberry. The open reading frame of FaSOC1 was 648bp, encoding a protein of 215 amino acids. Sequence alignment and phylogenetic analysis showed that the FaSOC1 protein contained a highly conserved MADS domain and a SOC1 motif, and that it was a member of the SOC1-like genes of dicots. The FaSOC1 protein mainly localized in the cytoplasm of onion epidermal cells and Arabidopsis protoplasts, and showed no transcriptional activation activity in yeast cells. Under the floral induction conditions, the expression of FaSOC1 increased during the first 2weeks of short-day treatment, but declined dramatically during three to 4weeks. FaSOC1 was highly expressed in reproductive organs, including shoot apices, floral buds, flowers, stamens and sepals. Overexpression of FaSOC1 in wild-type Arabidopsis caused early flowering and upregulated the expression of flowering time genes LFY and AP1. In addition, the yeast two-hybrid and BiFC assays confirmed that FaSOC1 could interact with AGL24. In conclusion, these results suggest that FaSOC1 is a flowering promoter in strawberry.

Isolation and characterization of dehydration-responsive element-binding factor 2C (MsDREB2C) from Malus sieversii Roem.

DREB2 (dehydration-responsive element-binding factor 2)-type transcription factors play a critical role in the stress-related regulation network in plants. In this study, we isolated and characterized a DREB2 homolog from Malus sieversii Roem., designated MsDREB2C (GenBank accession No. JQ790526). MsDREB2C localized to the nucleus and transactivated reporter genes in yeast strain YGR-2. Quantitative real-time PCR analysis demonstrated that MsDREB2C was constitutively expressed and significantly induced by drought, salt, cold, heat and ABA. Transgenic Arabidopsis plants overexpressing MsDREB2C exhibited increased root and leaf growth and proline levels, and reduced water loss and stomatal aperture. The transcriptional level of genes that function downstream of dehydration-responsive elements was greater in the transgenic Arabidopsis plants than in wild-type plants under control and abiotic stress conditions. Furthermore, constitutive expression of MsDREB2C repressed the expression of pathogenesis-related (PR) genes and the activity of peroxidase in transgenic plants under control and pathogenic conditions. As a result, transgenic plants were more tolerant to drought, heat and cold, but more sensitive to Pst DC3000 (Pseudomonas syringae pv . tomato DC3000) infection than control plants. ß-Glucuronidase expression analysis of the MsDREB2C promoter in transgenic tobacco plants showed that MsDREB2C was mainly expressed in the vascular tissues and seeds. Deletion analysis identified the regulatory regions responsible for the plant's response to drought (-831 to -680), ABA (-831 to -680 and -335 to -148), salt (-831 to -335), cold (-1,317 to -831 and -335 to -148) and heat (-335 to -148).

Genome-wide analysis of the GH3 family in apple (Malus × domestica).

BACKGROUND: Auxin plays important roles in hormone crosstalk and the plant's stress response. The auxin-responsive Gretchen Hagen3 (GH3) gene family maintains hormonal homeostasis by conjugating excess indole-3-acetic acid (IAA), salicylic acid (SA), and jasmonic acids (JAs) to amino acids during hormone- and stress-related signaling pathways. With the sequencing of the apple (Malus × domestica) genome completed, it is possible to carry out genomic studies on GH3 genes to indentify candidates with roles in abiotic/biotic stress responses. RESULTS: Malus sieversii Roem., an apple rootstock with strong drought tolerance and the ancestral species of cultivated apple species, was used as the experimental material. Following genome-wide computational and experimental identification of MdGH3 genes, we showed that MdGH3s were differentially expressed in the leaves and roots of M. sieversii and that some of these genes were significantly induced after various phytohormone and abiotic stress treatments. Given the role of GH3 in the negative feedback regulation of free IAA concentration, we examined whether phytohormones and abiotic stresses could alter the endogenous auxin level. By analyzing the GUS activity of DR5::GUS-transformed Arabidopsis seedlings, we showed that ABA, SA, salt, and cold treatments suppressed the auxin response. These findings suggest that other phytohormones and abiotic stress factors might alter endogenous auxin levels. CONCLUSION: Previous studies showed that GH3 genes regulate hormonal homeostasis. Our study indicated that some GH3 genes were significantly induced in M. sieversii after various phytohormone and abiotic stress treatments, and that ABA, SA, salt, and cold treatments reduce the endogenous level of axuin. Taken together, this study provides evidence that GH3 genes play important roles in the crosstalk between auxin, other phytohormones, and the abiotic stress response by maintaining auxin homeostasis.