Xyloglucan endotransglycosylase/hydrolase (XTH) is a cell-wall-modifying enzyme participating in diverse cell morphogenetic processes and adaptation to stress. In this study, 48 XTH genes were identified from two pineapple (Ananas comosus) cultivars (‘F153’ and ‘MD2’) and designated Ac(F153)XTH1 to -24 and Ac(MD2)XTH1 to -24 based on their orthology with Arabidopsis thaliana genes. Endoglucanase family 16 members were identified in addition to XTHs of glycoside hydrolase family 16. Phylogenetic analysis clustered the XTHs into three major groups (Group I/II, III and Ancestral Group) and Group III was subdivided into Group IIIA and Group IIIB. Similar gene structure and motif number were observed within a group. Two highly conserved domains, glycosyl hydrolase family 16 (GH16-XET) and xyloglucan endotransglycosylase C-terminus (C-XET), were detected by multiple sequences alignment of all XTHs. Segmental replication were detected in the two cultivars, with only the paralogous pair Ac(F153)XTH7-Ac(F153)XTH18 presented in ‘F153’ prior to genomic expansion. Transcriptomic analysis indicated that XTHs were involved in the regulation of fruit ripening and crassulacean acid metabolism with tissue specificity and quantitative real-time PCR analysis suggested that Ac(MD2)XTH18 was involved in root growth. The results enhance our understanding of XTHs in the plant kingdom and provide a basis for further studies of functional diversity in A. comosus.

Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.

Background: The dysregulation of autophagy and immunological processes has been linked to various pathophysiological conditions, including cancer. Most notably, their particular involvement in hepatocellular carcinoma (HCC) is becoming increasingly evident. This has led to the possibility of developing a prognostic signature based on immuno-autophagy-related (IAR) genes. Given that long non-coding RNAs (lncRNAs) also play a special role in HCC, a combined signature utilizing IAR genes and HCC-associated long noncoding RNAs (as IARlncRNA) may potentially help in the clinical scenario. Method: We used Pearson correlation analysis, Kaplan–Meier survival curves, univariate and multivariate Cox regression, and ROC curves to generate and validate a prognostic immuno-autophagy-related long non-coding RNA (IARlncRNA) signature. The Chi-squared test was utilized to investigate the correlation between the obtained signature and the clinical characteristics. CIBERSORT algorithms and the Wilcoxon rank sum test were applied to investigate the correlation between signature and infiltrating immune cells. GO and KEGG analyses were performed to derived signature-dependent pathways. Results: Herein, we build an IAR-lncRNA signature (as first in the literature) and demonstrate its prognostic ability in hepatocellular carcinoma. Primarily, we identified three IARlncRNAs (MIR210HG, AC099850.3 and CYTOR) as unfavorable prognostic determinants. The obtained signature predicted the high-risk HCC group with shorter overall survival, and was further associated with clinical characteristics such as tumor grade (t = 10.918, p = 0.001). Additionally, several infiltrating immune cells showed varied fractions between the low-risk group and the high-risk HCC groups in association with the obtained signature. In addition, pathways analysis described by the signature clearly distinguishes both risk groups in HCC. Conclusions: The immuno-autophagy-related long non-coding RNA (IARlncRNA) signature we established exhibits a prognostic ability in hepatocellular carcinoma. To our knowledge, this is the first attempt in the literature to combine three determinants (immune, autophagy and LnRNAs), thus requiring molecular validation of this obtained signature in clinical samples.

N6-methyladenosine (m6A) is the most prevalent and internal modification that occurs in the messenger RNAs of eukaryotes. However, knowledge of the impact of these modifications on gene expression regulation remains limited. By using the in vitro MeRIP-seq and RNA-seq assays, we discovered that the mRNA demethylase FTO was significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and cells. Knockdown of FTO drastically suppressed the proliferation, migration, and invasion of ESCC cells. Furthermore, by using transcriptome-wide m6A-seq and RNA-seq assays, we identified ERBB2 is the target of FTO, which acts in concert in ESCC tumorigenesis and metastasis. Moreover, loss and gain functional studies suggested that the m6A reader YTHDF1 stabilizes ERBB2 mRNA via decoding the m6A modification. All these results uncovered a new signaling cascade, including FTO, YTHDF1, and ERBB2, which finely regulates the ESCC progression.

Epigenetic regulation plays a critical role in the development, progression, and treatment of tumors. The most common chemical modification of mRNA, called m6A, is essential for controlling mRNA stability, splicing, and translation. Methyltransferase-like 3 (METTL3) is an important m6A methyltransferase. The mechanism of action of METTL3 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this investigation, we sought to clarify the function and clinical importance of METTL3 in ESCC and investigate its underlying mechanisms. We discovered that METTL3 has a significant proliferative effect in ESCC cells by using lentiviral construction of stable cell lines overexpressing METTL3 (METTL3-OE) and knocking down METTL3 (sh-METTL3). To create a xenograft tumor model, we inoculated KYSE510 cells subcutaneously into BALB/c nude mice and discovered that sh-METTL3 inhibited the tumorigenicity of esophageal cancer KYSE510 cells in the nude mouse tumor model. MeRIP-seq and RNA-seq analysis revealed IFIT2 to be a METTL3 target gene. The findings revealed that METTL3 regulates IFIT2 and thus influences malignant biological behaviors such as proliferation, migration, and invasion of ESCC, as well as the immune microenvironment of tumors.