scholarly journals SNAI2-Induced CircMTO1 Promotes Cell Proliferation and Inhibits Apoptosis Through the miR-320b/MCL1 Axis in Human Granulosa-Like Tumor Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Duan ◽  
Hongning Cai ◽  
Yanming Huang ◽  
Liangyan Shi
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
The Novel ◽  
High Prevalence ◽  
Snail Family ◽  
Series Of Experiments

Polycystic ovary syndrome (PCOS), one of the most common types of endocrine diseases, is characterized by a high prevalence among women of reproductive-age. However, its pathogenesis and molecular mechanisms remain unclear. CircMTO1 has been reported to participate in numerous biological processes, but, its role in PCOS progression remains unknown. In the current study, we elucidated the expression and circRNA characterization of circMTO1 in human granulosa-like tumor cells. We found that circMTO1 knockdown promoted human granulosa-like tumor cell proliferation and inhibited its apoptosis rate. Next, we explored the underlying molecular mechanisms by using a series of experiments. Our results revealed the effect of the novel circMTO1/miR-320b/MCL1 axis in human granulosa-like tumor cells. Furthermore, we found that the expression of circMTO1 was induced by Snail family transcriptional repressor 2 (SNAI2) in human granulosa-like tumor cells. Our results may provide potential targets for PCOS research and a novel direction for the diagnosis and treatment of PCOS.

scholarly journals Beyond Alkaloids: Novel Bioactive Natural Products From Lobelia Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Qinfang Zheng ◽  
Ye Wang ◽  
Shuihan Zhang
Keyword(s):  
Molecular Mechanisms ◽  
The Novel ◽  
Bioactive Components ◽  
Research Focus ◽  
Bioactive Natural Products ◽  
Hyperactivity Disorder ◽  
Multicenter Phase ◽  
Major Shift ◽  
Significant Attention

In this work, we reviewed the progress in the phytochemical and biological investigations of bioactive components derived from medicinally valuable Lobelia species. In the last 60 years, Lobelia has garnered significant attention from the phytochemist from around the world, majorly due to the discovery of bioactive piperidine alkaloids (e.g., lobinaline and lobeline) in the early 1950s. Later, lobeline underwent clinical trials for several indications including the treatment of attention deficit hyperactivity disorder and a multicenter phase three trial for smoking cessation. Subsequently, several other alkaloids derived from different species of Lobelia were also investigated for their pharmacological characteristics. However, in the last few years, the research focus has started shifting to the characterization of the other novel chemical classes. The major shift has been noticed due to the structurally similar alkaloid components, which essentially share similar pharmacological, physicochemical, and toxicological profiles. In this review, we present an up-to-date overview of their progress with special attention to understanding the molecular mechanisms of the novel bioactive components.

scholarly journals Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ethan P. Metz ◽  
Erin L. Wuebben ◽  
Phillip J. Wilder ◽  
Jesse L. Cox ◽  
Kaustubh Datta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cell Cycle Machinery

Abstract Background Quiescent tumor cells pose a major clinical challenge due to their ability to resist conventional chemotherapies and to drive tumor recurrence. Understanding the molecular mechanisms that promote quiescence of tumor cells could help identify therapies to eliminate these cells. Significantly, recent studies have determined that the function of SOX2 in cancer cells is highly dose dependent. Specifically, SOX2 levels in tumor cells are optimized to promote tumor growth: knocking down or elevating SOX2 inhibits proliferation. Furthermore, recent studies have shown that quiescent tumor cells express higher levels of SOX2 compared to adjacent proliferating cells. Currently, the mechanisms through which elevated levels of SOX2 restrict tumor cell proliferation have not been characterized. Methods To understand how elevated levels of SOX2 restrict the proliferation of tumor cells, we engineered diverse types of tumor cells for inducible overexpression of SOX2. Using these cells, we examined the effects of elevating SOX2 on their proliferation, both in vitro and in vivo. In addition, we examined how elevating SOX2 influences their expression of cyclins, cyclin-dependent kinases (CDKs), and p27Kip1. Results Elevating SOX2 in diverse tumor cell types led to growth inhibition in vitro. Significantly, elevating SOX2 in vivo in pancreatic ductal adenocarcinoma, medulloblastoma, and prostate cancer cells induced a reversible state of tumor growth arrest. In all three tumor types, elevation of SOX2 in vivo quickly halted tumor growth. Remarkably, tumor growth resumed rapidly when SOX2 returned to endogenous levels. We also determined that elevation of SOX2 in six tumor cell lines decreased the levels of cyclins and CDKs that control each phase of the cell cycle, while upregulating p27Kip1. Conclusions Our findings indicate that elevating SOX2 above endogenous levels in a diverse set of tumor cell types leads to growth inhibition both in vitro and in vivo. Moreover, our findings indicate that SOX2 can function as a master regulator by controlling the expression of a broad spectrum of cell cycle machinery. Importantly, our SOX2-inducible tumor studies provide a novel model system for investigating the molecular mechanisms by which elevated levels of SOX2 restrict cell proliferation and tumor growth.

Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

2001 ◽  
Vol 28 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Mitsuyoshi Yoshimoto ◽  
Atsuo Waki ◽  
Yoshiharu Yonekura ◽  
Norihiro Sadato ◽  
Tetsuhito Murata ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Acetate Metabolism

scholarly journals Identification and characterization of novel porcine astroviruses (PAstVs) with high prevalence and frequent co-infection of individual pigs with multiple PAstV types

2013 ◽  
Vol 94 (3) ◽  
pp. 570-582 ◽  
Author(s):  
Chao-Ting Xiao ◽  
Luis G. Giménez-Lirola ◽  
Priscilla F. Gerber ◽  
Yong-Hou Jiang ◽  
Patrick G. Halbur ◽  
...  
Keyword(s):  
Zoonotic Potential ◽  
The Novel ◽  
Extraintestinal Manifestations ◽  
Faecal Samples ◽  
High Prevalence ◽  
The Usa ◽  
History Of ◽  
Identification And Characterization ◽  
Sequence Identities

Many astrovirus (AstV) species are associated with enteric disease, although extraintestinal manifestations in mammalian and avian hosts have also been described. In this study, the prevalence rates of porcine AstV types 1–5 (PAstV1–PAstV5) were investigated using faecal samples from 509 pigs of which 488 (95.9 %) came from farms with a history of diarrhoea. All of the five known PAstV types were found to circulate in pigs in the USA, and co-infection of a single pig with two or more PAstV types was frequently observed. A high overall prevalence of 64.0 % (326/509) of PAstV RNA-positive samples was detected, with 97.2 % (317/326) of the PAstV RNA-positive pigs infected with PAstV4. Further genomic sequencing and characterization of the selected isolates revealed low sequence identities (49.2–89.0 %) with known PAstV strains, indicating novel types or genotypes of PAstV2, PAstV4 and PAstV5. Some new features of the genomes of the PAstVs were also discovered. The first complete genome of a PAstV3 isolate was obtained and showed identities of 50.5–55.3 % with mink AstV and the novel human AstVs compared with 38.4–42.7 % with other PAstV types. Phylogenetic analysis revealed that PAstV1, PAstV2 and PAstV3 were more closely related to AstVs from humans and other animals than to each other, indicating past cross-species transmission and the zoonotic potential of these PAstVs.

scholarly journals Roles of Oxidative Stress in Policystic Ovary Syndrome

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Marija Bicanin Ilic ◽  
Aleksandra Dimitrijevic ◽  
Igor Ilic
Keyword(s):  
Oxidative Stress ◽  
Polycystic Ovary ◽  
Signs And Symptoms ◽  
Reproductive Age ◽  
The Novel ◽  
Ovary Syndrome ◽  
Total Antioxidative Capacity ◽  
Definition Of ◽  
Insuline Resistance ◽  
Oxidative Biomarkers

Abstract Polycystic ovary syndrome (PCOS) represent a common endocrine disorder that affects nearly 4 to 12 percents of reproductive age women in general population studies (1). PCOS is caracterized by the oligoovulation or anovulation, hyperandrogenisam and multiple small ovarian cysts. The etiology of PCOS is steel unclear. Patophysiology of PCOS represents the complex mehanism. There is a wide spectar of signs and symptoms of the PCOS, which vary in severity over the time and within individuals. Major symptoms are: the amenhorhea, oligomenorhea combined with of episodes of menometrorhagia. Some signs of hiperandrogenism are: acne, hirsutism and alopecia. Other important symptoms of the PCOS are: the obesity, dyslpedemia, insuline resistance, metabolic syndrome, infertility, endometrial neoplasia, pregnancy loss. Diagnosis is achieved by exclusion of other factors that lead to anovulation, and laboratory assay of sex hormones and gonadotropines. One of the novel approaches in evaluation of etiology and pathogenesis of the PCOS recognizes oxidative stress as an important factor in genesis of this syndrome. For investigation of the oxidative stress role in the pathogenesis of diseases, some biochemical markers have been used including the MDA and NO also anti-oxidative biomarkers such as Total Antioxidative Capacity, Superoxide Dismutase, Glutation Peroxidase, and glutathione. Most of recent studies compared the oxidative stress biomarker level or antioxidative biomarkers levels in the PCOS patients and healthy controls. Patients with the PCOS in those studies were often subdivided in groups by the presence of insulin resistance (HOMA index) or infertility or not. One of the main problems in this field of research is inconsistency in precise definition of the PCOS, as well as different expression of various symptoms within individuals over the time. In that manner it is very difficult to follow up these patients and to establish criteria that could be compared in studies.

Do mycoplasmas cause human cancer?

2001 ◽  
Vol 47 (8) ◽  
pp. 691-697 ◽  
Author(s):  
Nevio Cimolai
Keyword(s):  
Tissue Culture ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Epidemiological Studies ◽  
Respiratory Pathogen ◽  
The Novel ◽  
The 1960S ◽  
In Vitro Data

A linkage between mycoplasmas and malignancy was mainly proposed in the 1960s when human-associated mycoplasmas were becoming of interest given the novel characterization of the human respiratory pathogen Mycoplasma pneumoniae. Associations with leukemia and other malignancies, however, were largely ascribed to tissue-culture contamination, which is now recognized as a significant potential problem in molecular biology circles. A few epidemiological studies, however, continue to raise concern over such a linkage. As well, in vitro data have demonstrated the potential for some mycoplasmas to induce karyotypic changes and malignant transformation during chronic tissue-culture infestation. As cellular and molecular mechanisms for such transformation become studied, a resurgence of interest in this area is inevitable. A role for mycoplasmas in malignancy of any sort is conjectural, but there remains a need to continue with focussed epidemiological and laboratory investigations.Key words: mycoplasma, cancer, oncogenesis, leukemia.

scholarly journals Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1096
Author(s):  
Zhe Kong ◽  
Yali Lu ◽  
Xuechao Wan ◽  
Jun Luo ◽  
Dujian Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
The Novel ◽  
Cancer Tissues ◽  
Posttranscriptional Level

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

scholarly journals miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS

Reproduction ◽  
2018 ◽  
Author(s):  
Lihua Yao ◽  
Mingyang Li ◽  
Jingwen Hu ◽  
Wangsheng Wang ◽  
Minzhi Gao
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Antral Follicle ◽  
Reproductive Age ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Total Testosterone ◽  
Human Follicular Fluid ◽  
Pcos Group

Polycystic ovary syndrome (PCOS) is a major cause of infertility in women of reproductive age. However, its exact etiology remains unknown. In this study, we sequenced microRNAs (miRNAs) in human follicular fluid and identified 16 downregulated and 3 upregulated miRNAs in PCOS group compared with non-PCOS group. Among the differential expressed miRNAs, miR-335-5p was verified lower abundance in PCOS than non-PCOS group using quantitative real-time polymerase chain reaction. Besides, miR-335-5p negatively correlated with antral follicle count, anti-Müllerian hormone, and total testosterone. Bioinformatics analysis identified serum/glucocorticoid regulated kinase family member 3 (SGK3) as a potential target gene of miR-335-5p. SGK3 is involved in protein kinase B-mammalian target of rapamycin kinase (AKT-mTOR) signaling pathway and cell proliferation. Western blotting and cell counting kit-8 assays demonstrated that miR-335-5p mimic reduced, while miR-335-5p inhibitor increased, SGK3 abundance, AKT-mTOR pathway and cell proliferation in human granulosa-like tumor KGN cells. Dual-luciferase reporter assays showed that miR-335-5p binds to the 3 untranslated region of SGK3 mRNA. Furthermore, miR-335-5p was decreased and SGK3 was elevated in human granulosa cells obtained from PCOS patients as compared with non-PCOS controls. These findings suggested that miR-335-5p is involved in granulosa cells proliferation via reducing SGK3 expression, which might provide a molecular target to improve dysfunctional granulosa cells in patients with PCOS.

scholarly journals Lnc-GULP1-2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization​

2021 ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Protein Coding ◽  
Ovarian Follicle Development ◽  
Multiple Cell ◽  
Ovarian Follicular Development

Abstract Backgrounds: Long non-coding RNA is a novel group of non-protein coding transcripts over 200nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1-2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1-2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. Conclusions: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.

Isolation and characterization of an acute promyelocytic leukemia cell line selectively resistant to the novel antileukemic and apoptogenic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2672-2682 ◽  
Author(s):  
Isabella Ponzanelli ◽  
Maurizio Giannı̀ ◽  
Raffaella Giavazzi ◽  
Angela Garofalo ◽  
Ines Nicoletti ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Molecular Mechanisms ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
The Novel ◽  
Isolation And Characterization

6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) is a novel compound that represents the prototype of a new class of synthetic retinoids with apoptogenic properties in acute promyelocytic leukemia (APL) and other types of leukemia. In this article, using SCID mice xenografted with APL-derived NB4 cells, we demonstrate that CD437 has significant antileukemic activity in vivo. In addition, we report on the isolation and characterization of an APL cell line (NB4.437r) resistant to CD437. The cell line retains expression of PML-RAR and is approximately 33-fold more resistant than the parental counterpart to the apoptogenic effects of the retinoid. Resistance is relatively specific to CD437 and structural congeners because the NB4.437r cell line is still sensitive to various types of apoptogenic compounds. The CD437-resistant cell line maintains sensitivity to the antiproliferative and apoptotic action of all-trans-retinoic acid, AM580, and fenretinide, though it shows partial resistance to the cytodifferentiating effects of the first 2 compounds. Resistance to CD437 lays upstream of the CD437-induced release of cytochrome c from the mitochondria and the activation of caspase-3, -7, -8, and -9. Furthermore, NB4.437r cells are deficient in the CD437-dependent activation of nuclear NFkb and AP1-binding activities and in the phosphorylation of the protein kinase Akt. In the case of AP1, deficient assembly of the complex is not caused by the lack of activation of the Jun N-terminal kinase (JNK) family of kinases. The novel cell line will be useful in the elucidation of the molecular mechanisms underlying the apoptogenic action of CD437 and structurally related retinoids.

Sign in / Sign up

Export Citation Format

Share Document