Altered Expression of GJD2 Messenger RNA and the Coded Protein Connexin 36 in Negative Lens–induced Myopia of Guinea Pigs

Abstract Background Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. Results To investigate the alterations of microRNA profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expression of differentially expressed microRNAs. As a result, we successfully established an NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. Conclusions Our findings indicate that the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.

Download Full-text

Altered expression and distribution of intercalated diskassociated proteins in guinea pigs with pressure-overloaded cardiac hypertrophy and failure

Journal of Cardiac Failure ◽

10.1016/s1071-9164(98)90059-8 ◽

1998 ◽

Vol 4 (3) ◽

pp. 16

Author(s):

Xuejun Wang ◽

A.Martin Gerdes

Keyword(s):

Cardiac Hypertrophy ◽

Guinea Pigs ◽

Altered Expression

Download Full-text

Altered Expression of miR-146a-5p and Bcl-2 in Oncocytic Carcinoma of the Breast: A Case Report

10.21203/rs.3.rs-659177/v1 ◽

2021 ◽

Author(s):

Yumiko Koi ◽

Yuki Yamamoto ◽

Saori Fukunaga ◽

Tatsunari Sasada ◽

Keiko Kajitani ◽

...

Keyword(s):

Messenger Rna ◽

Molecular Profile ◽

Control Group ◽

Carcinoma Of The Breast ◽

Altered Expression ◽

Case Presentation ◽

Oncocytic Carcinoma ◽

Granular Eosinophilic Cytoplasm ◽

Eosinophilic Cytoplasm ◽

Cystic Disease Fluid Protein

Abstract Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.

Download Full-text

Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs

Journal of Endocrinology ◽

10.1677/joe.1.05781 ◽

2005 ◽

Vol 184 (1) ◽

pp. 179-189 ◽

Cited By ~ 26

Author(s):

A M Carter ◽

M J Kingston ◽

K K Han ◽

D M Mazzuca ◽

K Nygard ◽

...

Keyword(s):

Amniotic Fluid ◽

Guinea Pigs ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Altered Expression ◽

Intrauterine Growth ◽

Fetal Plasma ◽

Fetal Tissues ◽

Igf Binding ◽

Igfbp 3

The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth. We hypothesized that intrauterine growth restriction (IUGR) in guinea pigs is mediated by the altered expression of IGFs and/or IGF binding protein (BP) mRNAs in tissues and is related to growth of specific tissues. IUGR was induced by unilateral uterine artery ligation on day 30 of gestation, and fetal plasma, amniotic fluid and tissue samples were collected at 55–57 days (term about 68 days) from paired IUGR and control fetuses (n=6). Western ligand blotting and immunoblotting were used to compare IGFBP levels in plasma and amniotic fluid. Total RNA was extracted from placenta and fetal tissues, and the relative abundance of IGF-II and IGFBP-1–6 mRNA was determined by Northern blotting, using species-specific probes where available. IUGR fetuses had decreased (P<0.01, by Student’s t-test) placental weight and body weight with an increase in the brain:liver weight ratio. The principal IGFBPs in fetal plasma migrated at 40–35, 30 and 25 kDa and were identified as IGFBP-3, -2 and -4 respectively. IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels. IGFBPs were detected at low levels in amniotic fluid of control fetuses but at higher levels in IUGR fetuses. In IUGR placentae, there was a small increase in IGFBP-4 mRNA (P<0.05). IGFBP-2 mRNA increased (P<0.001) in liver of IUGR fetuses. IGF-II and IGFBP mRNA expression did not change in fetal muscle. The results are consistent with reduced IGF action, directly or through inhibition by IGFBPs, particularly by circulating and tissue IGFBP-2, as a potential causal factor in decreased growth of the placenta and certain fetal tissues.

Download Full-text

Alternative Splicing: Expanding the Landscape of Cancer Biomarkers and Therapeutics

International Journal of Molecular Sciences ◽

10.3390/ijms21239032 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9032

Author(s):

Cláudia Bessa ◽

Paulo Matos ◽

Peter Jordan ◽

Vânia Gonçalves

Keyword(s):

Alternative Splicing ◽

Messenger Rna ◽

Human Cancer ◽

Genetic Alterations ◽

Altered Expression ◽

Genome Wide ◽

Human Genes ◽

Transcriptional Regulatory Mechanism ◽

A Genome ◽

Wide Scale

Alternative splicing (AS) is a critical post-transcriptional regulatory mechanism used by more than 95% of transcribed human genes and responsible for structural transcript variation and proteome diversity. In the past decade, genome-wide transcriptome sequencing has revealed that AS is tightly regulated in a tissue- and developmental stage-specific manner, and also frequently dysregulated in multiple human cancer types. It is currently recognized that splicing defects, including genetic alterations in the spliced gene, altered expression of both core components or regulators of the precursor messenger RNA (pre-mRNA) splicing machinery, or both, are major drivers of tumorigenesis. Hence, in this review we provide an overview of our current understanding of splicing alterations in cancer, and emphasize the need to further explore the cancer-specific splicing programs in order to obtain new insights in oncology. Furthermore, we also discuss the recent advances in the identification of dysregulated splicing signatures on a genome-wide scale and their potential use as biomarkers. Finally, we highlight the therapeutic opportunities arising from dysregulated splicing and summarize the current approaches to therapeutically target AS in cancer.

Download Full-text

Blockade of Fas-dependent apoptosis by soluble Fas in LGL leukemia

Blood ◽

10.1182/blood.v100.4.1449.h81602001449_1449_1453 ◽

2002 ◽

Vol 100 (4) ◽

pp. 1449-1453 ◽

Cited By ~ 64

Author(s):

Jin Hong Liu ◽

Sheng Wei ◽

Thierry Lamy ◽

Yongxiang Li ◽

P.K. Epling-Burnette ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Messenger Rna ◽

Fas Ligand ◽

Leukemic Cells ◽

Apoptosis Resistance ◽

Apoptotic Pathway ◽

Altered Expression ◽

Soluble Fas ◽

Fas Signaling ◽

Lgl Leukemia

Altered expression of the Fas-Fas ligand apoptotic pathway leads to lymphoproliferative and autoimmune diseases. Inlpr/lpr mice and children with autoimmune lymphoproliferative syndrome, defective apoptosis is due to Fas mutations. Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disorder associated with rheumatoid arthritis. Leukemic LGLs are resistant to Fas-dependent apoptosis despite expressing high levels of Fas. Such resistance can be overcome by activating leukemic LGLs in vitro, suggesting inhibition of Fas signaling in leukemic cells. We report that sera from patients with LGL leukemia contain high levels of soluble Fas. Ten of these 33 patients with LGL leukemia also had rheumatoid arthritis. Cloning and sequencing revealed expression of multiple Fas messenger RNA variants in leukemic LGL. These Fas variants, including 3 newly described here, encode soluble Fas molecules. Supernatants from cells transfected with these Fas variants blocked Fas-dependent apoptosis of leukemic LGLs. These results suggest that blockade of Fas-signaling by soluble Fas may be a mechanism leading to apoptosis resistance in leukemic LGLs.

Download Full-text

Enhanced Expression of Sulfatide, a Sulfated Glycolipid, in Well-Differentiated Endometrial Adenocarcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31825f639f ◽

2012 ◽

Vol 22 (7) ◽

pp. 1192-1197 ◽

Cited By ~ 7

Author(s):

Taro Sugiyama ◽

Masaki Miyazawa ◽

Mikio Mikami ◽

Yumiko Goto ◽

Yoshihiro Nishijima ◽

...

Keyword(s):

Messenger Rna ◽

Immunohistochemical Staining ◽

Endometrial Adenocarcinoma ◽

Response To Therapy ◽

Rna Expression ◽

Cholesterol Sulfate ◽

Altered Expression ◽

Tumor Tissues ◽

Poorly Differentiated ◽

Well Differentiated

ObjectivesIt is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma.Materials and MethodsWe determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining.ResultsNo significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas.ConclusionThese findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.

Download Full-text

Altered expression of NDST-1 messenger RNA in puromycin aminonucleoside nephrosis

Journal of Laboratory and Clinical Medicine ◽

10.1016/j.lab.2003.10.012 ◽

2004 ◽

Vol 143 (2) ◽

pp. 106-114 ◽

Cited By ~ 9

Author(s):

Kenji Nakayama ◽

Yumiko Natori ◽

Toshinobu Sato ◽

Tomoyoshi Kimura ◽

Akira Sugiura ◽

...

Keyword(s):

Messenger Rna ◽

Puromycin Aminonucleoside ◽

Altered Expression ◽

Aminonucleoside Nephrosis ◽

Puromycin Aminonucleoside Nephrosis

Download Full-text

Altered Expression of MLH1, MSH2, and MSH6 in Predisposition to Hereditary Nonpolyposis Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2003.03.181 ◽

2003 ◽

Vol 21 (19) ◽

pp. 3629-3637 ◽

Cited By ~ 65

Author(s):

Elise Renkonen ◽

Yange Zhang ◽

Hannes Lohi ◽

Reijo Salovaara ◽

Wael M. Abdel-Rahman ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Mrna Expression ◽

Messenger Rna ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Population Based ◽

Altered Expression ◽

Dna Mismatch ◽

Mmr Genes ◽

Hereditary Nonpolyposis

Purpose: A considerable fraction (30% to 70%) of families with verified or putative hereditary nonpolyposis colorectal cancer fails to show mutations in DNA mismatch repair (MMR) genes. Our purpose was to address the genetic etiology of such families. Materials and Methods: We scrutinized a population-based cohort of 26 families from Finland that had screened mutation-negative by previous techniques. Blood was tested for allelic messenger RNA (mRNA) expression of MLH1, MSH2, and MSH6 by single nucleotide primer extension (SNuPE), and tumor tissue for MMR protein expression by immunohistochemistry (IHC) as well as for microsatellite instability (MSI). Full-length cDNAs of genes implicated by SNuPE or IHC were cloned and sequenced. Results: Unbalanced mRNA expression of MLH1 alleles was evident in two families. An inherited nonsense mutation was subsequently identified in one family, and complete silencing of the mutated allele was identified in the other family. Extinct protein expression by IHC implicated MLH1 in these two and in four other families, MSH2 in four families, and MSH6 in one family. Although no unequivocal genomic mutations were detected in the latter families, haplotype and other findings provided support for heritable defects. With one exception, all tumors with IHC alterations showed MSI, in contrast to the remaining families, which showed neither IHC changes nor MSI. Conclusion: Our expression-based strategy stratified the present “mutation-negative” cohort into two discrete categories: families linked to the major MMR genes MLH1, MSH2, and MSH6 (11 [42%] of 26) and those likely to be associated with other, as yet unknown susceptibility genes (15 [58%] of 26).

Download Full-text