scholarly journals Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Qiuyan Guo ◽  
Yan Cheng ◽  
Tian Liang ◽  
Yanan He ◽  
Chengcheng Ren ◽  
...  
Oncogene ◽  
2021 ◽  
Author(s):  
Jinguo Zhang ◽  
Wencai Guan ◽  
Xiaolin Xu ◽  
Fanchen Wang ◽  
Xin Li ◽  
...  

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.


2012 ◽  
Vol 22 (3) ◽  
pp. 457-464 ◽  
Author(s):  
Thijs Roelofsen ◽  
Léon C.L.T. van Kempen ◽  
Jeroen A.W.M. van der Laak ◽  
Maaike A. van Ham ◽  
Johan Bulten ◽  
...  

ObjectiveThe pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.MethodsCases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.ResultsNine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).ConclusionThis study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.


2021 ◽  
Vol 22 (12) ◽  
pp. 6216
Author(s):  
Monika Englert-Golon ◽  
Mirosław Andrusiewicz ◽  
Aleksandra Żbikowska ◽  
Małgorzata Chmielewska ◽  
Stefan Sajdak ◽  
...  

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.


2018 ◽  
Vol 14 (14) ◽  
pp. 2073-2082 ◽  
Author(s):  
You Wang ◽  
Zhicheng Zhou ◽  
Xinran Wang ◽  
Xuping Zhang ◽  
Yansu Chen ◽  
...  

Medicine ◽  
2020 ◽  
Vol 99 (47) ◽  
pp. e22777
Author(s):  
Hong-Yu Xu ◽  
Hua-Mei Song ◽  
Quan Zhou

2019 ◽  
Author(s):  
Na Li ◽  
Jiao Xiong ◽  
Zhengyu Li

Abstract Background: Homeobox B4 (HOXB4) is associated with the poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains to be determined. Methods:The Cancer Genome Atlas (TCGA) database indicated that high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed through a colony formation, migration, and invasion assay. The effect of HOXB4 on the expression of EMT and cancer stem cell markers was detected. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was performed in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results:Results showed that the expression of HOXB4 was higher in OV tissues than in normal tissues and correlated with the poor prognosis of OV. HOXB4 knockdown suppressed the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the up-regulation of HOXB4 in OV cells. The binding of two DNA motifs through HOXB4 regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in promoting tumor proliferation and metastasis was verified in mice. Further investigation revealed that HOXB4 triggered Snail and Zeb1 expression. Conclusion: Overall, HOXB4 overexpression was remarkably correlated with the poor prognosis of OV. HOXB4 up-regulated DHDDS, which co-contributed to the enhancer proliferation and invasion of OV cells, thus accelerating the malignant progression of OV.


2020 ◽  
Author(s):  
Shenglan Wang ◽  
Chuanchuan Liu ◽  
Yongchuan Li ◽  
Jinwan Qiao ◽  
Xinling Chen ◽  
...  

Abstract Objectives: The purpose of this study was to investigate the expression and clinical significance of LncRNA OIP5-AS1 in ovarian cancer , as well as its effect on malignant biological behavior of ovarian cancer cells. Methods: The expression of OIP5-AS1, miR-153-3p and KLF5 in ovarian cancer (OC) tissues and cells were detected by RT-qPCR. Western Blotting was used to detect KLF5 expression. The expression patterns of OIP5-AS1, U6 and GAPDH in nuclear and cytoplasm fractions were detected using qRT-PCR. Besides, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, The interaction between OIP5-AS1 and miR-153-3p and between miR-153-3p and KLF5 were verified by luciferase reporter assay, and the correlations among these three genes were analyzed.Results: OIP5-AS1 expression was up-regulated in ovarian cancer cell lines and tissues. Si-OIP5-AS1 inhibited cell proliferation, invasion and migration, and induced the apoptosis to a certain extent. Subcellular fraction assay revealed the location of OIP5-AS1 was mainly situated in the cytoplasm. In addition, miR-153-3p was a target of OIP5-AS1, and KLF5 was directly targeted by miR-153-3p. Si-OIP5-AS1 inhibited KLF5 expression, miR-153-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited OIP5-AS1 expression. Interestingly, expression of OIP5-AS1 and miR-153-3p, and expression of miR-153-3p and KLF5 were negatively correlated, while expression of OIP5-AS1 and KLF5 was positively correlated. In addition, si-KLF5 inhibited the malignant biological behavior of ovarian cancer cells, while miR-153-3p inhibitor had the opposite effect. Most importantly, the addition of si-OIP5-AS1 to mir-153-3p silenced cells could reverse the promotion effect of miR-153-3p inhibitor on the malignant biological behavior of ovarian cancer cells.Conclusions: OIP5-AS1 can be used as an effective prognostic indicator of ovarian cancer, which has the potential to be a new drug target.


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