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Purpose: Despite its recognized aggressive clinical manifestations, invasive micropapillary carcinoma has a controversial prognosis in comparison to invasive ductal carcinoma of the breast. This retrospective study aimed to explore the prognosis and underlying molecular mechanisms of invasive micropapillary carcinoma.

Methods: Through the SEER database, we compared patients survival outcomes with invasive micropapillary carcinoma versus invasive ductal carcinoma, and developed a nomogram to predict the overall survival of the former group. We explored gene profiles of invasive micropapillary carcinoma in the GEO database. Hub genes were identified as the top ten genes in the PPI network with the highest degrees of connectivity, and three of them were selected for validation by immunohistochemistry.

Results: Invasive micropapillary carcinoma patients had better overall survival and breast cancer-specific survival than invasive ductal carcinoma patients did. Multivariate analysis revealed age, marital status, TN stage, ER status, and chemotherapy as independent prognostic factors for invasive micropapillary carcinoma patients, which were used to construct a nomogram with good performance. A total of 294 DEGs were identified, with ten hub genes, including MMP2, FLNA and CFL1, which were expressed at lower levels in invasive micropapillary carcinoma patients than in invasive ductal carcinoma patients, indicating favorable outcomes.

Conclusions: Patients with invasive micropapillary carcinoma generally have a better prognosis than those with invasive ductal carcinoma does, which could be attributed to the lower expression of pro-oncogenic genes in the former group; however, the underlying mechanism needs further investigation.

Polycystic ovary syndrome (PCOS) is the leading cause of amenorrhea and anovulatory infertility in women of reproductive age. Both gene polymorphisms and tissue-specific epigenetic alterations, which determine gene transcription and translation dynamics in disease-states, strongly influence PCOS development. Particularly, promoter-proximal DNA methylation and microRNA expression changes show strong associations with follicular defects, suggesting post-transcriptional dysregulation of localized gene networks. Our recent methylome study and other studies, posit DNA methylation as a regulator of microRNA expression in PCOS. Here, we identified microRNAs, potentially regulated by DNA methylation, and investigated whether their altered expression influences target gene expression in the PCOS ovary. Using granulosa cell samples of women with PCOS and age-BMI matched controls, we evaluated the transcript levels of 14 microRNAs participating in different ovarian processes and assessed their CpG-DNA methylation levels. For 9 of these microRNAs, which revealed differential methylation consistent with their gene hypomethylation or hypermethylation profiles, we evaluated the expression of their predicted, proteincoding target transcripts. Our data indicated that microRNA hypermethylation and decreased transcription of miR-10b-5p, miR-127-3p, miR-5189, miR-410-3p and miR23a-3p were consistent with the upregulation of PTEN, MMP13, OLR1, TET3 and APAF1 in PCOS. Conversely, microRNA hypomethylation and increased expression of miR-140-5p, miR-182-3p, miR-200b-5p and miR-3687 were consistent with downregulation of FZD6, LRP6, ZEB1 and LDLR. However, these observations need robust validations in larger study cohorts complemented with functional and mechanistic studies. Overall, our study indicates that altered microRNA expression as a consequence of DNA methylation changes, may contribute to metabolic and reproductive dysfunction in PCOS.

Pre-existing of pulmonary tuberculosis (PTB) poses increased lung cancer risk, yet the molecular mechanisms remain inadequately understood. This study sought to elucidate the potential mechanisms by performing comprehensive analyses of differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from patients with PTB, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). Microarray assays were employed to analyze the DEGs in PBMCs of these patients. The analyses revealed that, compared to healthy controls, the number of differentially expressed LncRNA in PBMCs from patients with PTB, LUAD, and LUSC were 801, 8,541, and 7,796, respectively. Similarly, the differentially expressed mRNA in PBMCs from patients with PTB, LUAD, and LUSC were 629, 4,865, and 4,438, respectively. These differentially expressed transcripts represent significant resources for the identifying diagnostic and differential diagnostic biomarkers for lung cancer and PTB. Pathways enriched by dysregulated mRNAs in patients with PTB, LUAD, and LUSC were identified through GO and KEGG pathway analyses. The results indicated that 9 pathways including the NOD-like receptor signaling pathway, pathways in cancer, and the MAPK signaling pathway were co-enriched across the PTB, LUAD, and LUSC groups, providing insights into the mechanisms by which PTB may increase the risk of cancer development and progression.

In recent years, third-generation sequencing (TGS) technologies have transformed genomics and transcriptomics research, providing novel opportunities for significant discoveries. The long-read sequencing platforms, with their unique advantages over next-generation sequencing (NGS), including a definitive protocol, reduced operational time, and real-time sequencing, possess the potential to transform plant genomics. TGS optimizes and enhances the efficiency of data analysis by removing the necessity for time-consuming assembly tools. The current review examines the development and application of bioinformatics tools for data analysis and annotation, driven by the rapid advancement of TGS platforms like Oxford Nanopore Technologies and Pacific Biosciences. Transcriptome analysis utilizing TGS has been extensively employed to elucidate complex plant transcriptomes and genomes, particularly those characterized by high frequencies of duplicated genomes and repetitive sequences. As a result, current methodologies that allow for generating transcriptomes and comprehensive whole-genome sequences of complex plant genomes employing tailored hybrid sequencing techniques that integrate NGS and TGS technologies have been emphasized herein. This paper, thus, articulates a vision for a future in which TGS effectively addresses the challenges faced in plant research, offering a comprehensive understanding of its advantages, applications, limitations, and promising prospects.

Background: A comprehensive understanding of the molecular pathogenesis of chronic pancreatitis (CP), a fibroinflammatory disorder of the pancreas, is warranted for the development of targeted therapies. The current study focused on comparing the transcriptomes of pancreatic tissues obtained from patients with CP with those of two rodent models of chemically induced CP to identify dysregulated genes/signaling pathways.

Methods: Pancreatitis was induced in mice using cerulein and L-arginine. Pancreatic tissues were obtained from humans and mice. The RNA was isolated, and the transcriptomes were generated using the GeneChip Human Transcriptome Array 2.0 and Clariom D Mouse Array respectively. Differentially expressed genes with log2-fold changes ≥ +2 and ≤ -2 were considered for functional and signaling pathway enrichment analysis. The expression of NUCB2, which plays a role in β-cell function, was validated by ELISA in acute pancreatitis (AP) and immune cell responses in AP and CP using flow cytometry.

Results: The current study identifies L-arginine-induced CP as a better model for investigating the pathogenesis of human CP, with greater similarity in dysregulated genes (22%), transcription factors (34%) and enriched pathways (58%) compared to cerulein model (2%, 11% and 9%) respectively. Nesfatin-1, encoded by NUCB2, was decreased in patients with AP (12% nondiabetic, 41% post pancreatitis diabetes). The Th1 immune cell response was greater in the patients with AP (44%), whereas Th17 immune response was greater in patients with CP (18%).

Conclusion: Our study highlights potential novel and unexplored pathways involved in inflammation, fibrosis, and pain in CP and paves the way for testing them as putative drug targets using a severe disease model.

Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, LncRNA HOTAIR is closely related to MDR in lung cancer, however, the effects of HOTAIR on MRP1 expression and MDR in lung cancer cells (A549/DDP) remain unknown. In this study, the effects of HOTAIR on MRP1 gene expression and MDR in A549/DDP cells were monitored. LncRNA HOTAIR was upregulated in A549/DDP cells, and overexpression of HOTAIR promoted MRP1 expression and MDR development. The opposite trend was observed when HOTAIR was silenced in A549/DDP cells. To uncover the role of LncRNA HOTAIR in the MDR of human lung cancer, the effects of Egr1 on MRP1 gene expression and MDR in A549/DDP cells were monitored. The results showed that Egr1 could bind to the MRP1 promoter at site -53/-42 bp and regulate MRP1 expression. Egr1 knock-down reduced MRP1 expression, while Egr1 overexpression increased it. Further, the results demonstrated that LncRNA HOTAIR mediated the effects of Egr1 on MRP1 and MDR via sponging of miR-6807-3p. Moreover, miR-6807-3p exerts its function by targeting the Egr1 3'UTR. In conclusion, the results revealed the novel HOTAIR/miR-6807-3p/Egr1 axis in the regulation of MRP1 expression and MDR in lung cancer cells.

Glioblastoma, a type of brain tumor, is well-known for its aggressive nature and can affect individuals of all ages. Glioblastoma continues to be a difficult cancer to manage because of various resistance mechanisms. The blood-brain barrier restricts the delivery of drugs, and the heterogeneity of tumors, along with overlapping signaling pathways, complicates its effective treatment. Patients diagnosed with glioblastoma typically survive for no more than 2 years. Innovative therapies and early diagnostic tools for glioblastoma are essential. Circular RNAs have emerged as significant contributors to glioblastoma, and influence cancer mechanisms such as cell growth, death, invasion, and resistance to treatment. The circRNAs presence makes them essential candidates for treatment and practical diagnostic tools for glioblastoma. This review highlights the therapeutic approaches and diagnostic potential of circRNAs and explores their role in the molecular mechanisms underlying glioblastoma.

Liver cancer ranks as the sixth most prevalent form of cancer and stands as the fourth leading cause of cancer-related fatalities on a global scale. The two primary types of liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). While ICC originates from the bile ducts, HCC develops from hepatocytes, which are the primary functional cells of the liver. In cases where liver cancer is detected in its early stages, it can be effectively treated through locoregional interventions such as surgical resection, Radiofrequency Ablation, Transarterial chemoembolization, or liver transplantation. However, HCC is typically diagnosed at advanced stages, rendering these treatment options ineffective due to the unresectable nature of the tumor. LncRNAs, a novel class of RNA molecules and epigenetic regulators, have emerged as key players in the development and advancement of different types of tumors. They exert their influence by regulating the expression of downstream genes in cancer-related signaling pathways, thereby promoting the proliferation, migration, and invasion of tumor cells. Additionally, these transcripts have the ability to modify the activity and expression of tumor suppressors and oncogenes, further contributing to tumorigenesis. Recently, growing numbers of experiments have demonstrated the elevated expression of HOX antisense intergenic RNA (HOTAIR), a spliced and poly-adenylated lncRNA, in liver cancers and its association with cancer patient's prognosis and overall survival, as well as tumor cells' growth, metastasis, and resistance to therapies. This updated review will summarize molecular pathways by which lncRNA HOTAIR promotes liver cancer development, and highlight its diagnostic and therapeutic potential, though.

Sustainability in dairy cattle farms depends on the efficiency of milk yield and reproductive traits. Thus, this study aimed to investigate the effect of the FGF-2/Csp6I gene and major environmental factors on these traits in Holstein-Friesian cattle. A total of 212 whole blood samples were collected from the Vena coccygea of cattle and the data obtained from these samples were used in all statistical analyses. Then, the restriction fragment length polymorphism (RFLP) method (determination of genotypes) was conducted and programs including PopGene (allele and genotype frequencies), Minitab (association analyses) and MTDFREML (variance components and genetic parameters) were used. Alleles A (0.4269) and G (0.5731) as well as genotypes AA (0.174), AG (0.505) and GG (0.321) were found, indicating that the population is polymorphic and in Hardy-Weinberg equilibrium (P > 0.05). The effect of the Csp6I polymorphism of FGF-2 gene on peak milk yield (PMY) (P < 0.01); lactation milk yield (LMY), milking time (MT), 305-day and 200-day lactation milk yield (LMY₃₀₅ and LMY₂₀₀), average daily milk yield (ADMY) (P < 0.05); 100-day lactation milk yield (LMY₁₀₀), age of using in first breeding (AUFB) and number of inseminations per conception (NIPC) (P < 0.10) were significant. The heritability of milk yield traits and the correlation between direct and maternal heritability for reproductive traits were high. Furthermore, the breeding value of PMY was higher for the AA genotype (0.745 ± 0.292) than for the AG genotype (-0.268 ± 0.171) (P < 0.05). As a result, the A allele and AA genotype for the FGF-2/Csp6I gene had an increasing effect on milk yield without compromising reproductive performance in Holstein-Friesian dairy cattle.

Colon cancer is a leading cause of cancer-related deaths worldwide and has been increasingly linked to the gut microbiome. Clostridium butyricum (CB), a probiotic, has demonstrated potential in influencing colon cancer cell behavior, particularly through the modulation of long non-coding RNAs (lncRNAs) and mRNAs. This study examines the effects of CB on the expression of lncRNAs and mRNAs in SW480 colon cancer cells and their association with apoptosis. SW480 cells were co-cultured with CB, and total RNA was extracted for microarray analysis to identify differentially expressed lncRNAs and mRNAs. Quantitative real-time PCR and fluorescence staining were utilized to validate the expression changes of selected lncRNAs and to assess markers of apoptosis. Pathway enrichment analysis was performed to explore the biological functions of genes with altered expression. Co-culture with CB resulted in significant changes in lncRNA and mRNA expression, with 50 lncRNAs upregulated and 152 downregulated by more than five-fold. Similarly, 738 mRNAs were upregulated, while 1,088 were downregulated. Apoptosis analysis revealed that CB treatment induced apoptosis in SW480 cells, as evidenced by the upregulation of pro-apoptotic genes such as CASP1, TNF, and BNIP3L, and the downregulation of anti-apoptotic BCL family members. Pathway analysis suggested the involvement of the MAPK signaling pathway, cytokine-cytokine receptor interactions, and other pathways associated with tumor progression. These findings suggest that CB regulates the expression of lncRNAs and mRNAs involved in apoptosis and tumor progression, highlighting their potential as biomarkers and therapeutic targets in colorectal cancer. This study provides a novel therapeutic strategy for colon cancer treatment.