scholarly journals Investigation of olfactory receptor family 51 subfamily j member 1 (OR51J1) gene susceptibility as a potential breast cancer-associated biomarker

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246752
Author(s):  
Maryam Asadi ◽  
Nahid Ahmadi ◽  
Simin Ahmadvand ◽  
Ali Akbar Jafari ◽  
Akbar Safaei ◽  
...  

Among cancer treatment methods, targeted therapy using cancer-associated biomarkers has minimum side effects. Recently olfactory receptor (OR) family attracts the researcher’s attention as a favorable biomarker of cancer. Here, a statistical approach using complete data from the human protein atlas database was used to evaluate the potential of OR51J1 gene as a cancer-associated biomarker. To confirm the findings of statistical analysis, the OR51J1 mRNA and protein expression levels in breast tumor and normal tissue were measured using quantitative Real Time PCR (qRT-PCR) and immunohistochemistry (IHC) techniques. The association with clinicopathological factors was analyzed. Statistical analysis revealed that OR51J1 has a high expression level in more than 20 types of cancer tissues without any expression in 44 normal tissues. In 15 cancer types, including breast cancer, expression score was more than 90%. The qRT-PCR analysis in breast cancer showed OR51J1 have significantly higher expression level in tumors than normal tissues (2.91 fold). The IHC results showed OR51J1 expression on other cellular subtypes than tumor and normal cells, including myoepithelium, fibroblast, and lymphocytes. OR51J1 protein expression in invasive cells, as well as its overall score, showed a significant correlation with ER and PR expression and breast cancer (BC) subtypes. Results revealed the potential of OR51J1 as a cancer-associated biomarker for the diagnosis of breast cancer at the mRNA level.

Author(s):  
Wuping Yang ◽  
Kenan Zhang ◽  
Lei Li ◽  
Yawei Xu ◽  
Kaifang Ma ◽  
...  

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.


2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.


2016 ◽  
Vol 116 (9) ◽  
pp. 1512-1518 ◽  
Author(s):  
Lin Lu ◽  
Bin Chang ◽  
Xiudong Liao ◽  
Runlian Wang ◽  
Liyang Zhang ◽  
...  

AbstractThe present study was carried out to evaluate dietary Mn requirements of broilers from 22 to 42 d of age using molecular biomarkers. Chickens were fed a conventional basal maize–soyabean meal diet supplemented with Mn as Mn sulphate in graded concentrations of 20 mg Mn/kg from 0 to 140 mg Mn/kg of diet for 21 d (from 22 to 42 d of age). The Mn response curves were fitted for ten parameters including heart Mn-containing superoxide dismutase (MnSOD) mRNA and its protein expression levels and the DNA-binding activities of specificity protein 1 (Sp1) and activating protein-2 (AP-2). Heart MnSOD mRNA and protein expression levels showed significant quadratic responses (P<0·01), and heart MnSOD activity showed a broken-line response (P<0·01), whereas Mn content and DNA-binding activities of Sp1 and AP-2 in the heart displayed linear responses (P<0·01) to dietary Mn concentrations, respectively. The estimates of dietary Mn requirements were 101, 104 and 94 mg/kg for full expressions of MnSOD mRNA level, MnSOD protein level and MnSOD activity in the heart, respectively. Our findings indicate that heart MnSOD mRNA expression level is a more reliable indicator than heart MnSOD protein expression level and its activity for the evaluation of Mn requirement of broilers, and about 100 mg Mn/kg of diet is required for the full expression of heart MnSOD in broilers fed the conventional basal maize–soyabean meal diet from 22 to 42 d of age.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yanping Li ◽  
Shanshan Wang ◽  
Xiaoyuan Zhang ◽  
Rui Yang ◽  
Xiaonan Wei ◽  
...  

It was proven that PGK1 plays a vital role in the proliferation, migration, and invasion of human breast cancer. However, the correlation of PGK1 mRNA and protein expression with clinicopathologic characteristics and prognostic values according to various kinds of breast cancer patient classifications remains unsufficient. Here, we analyzed data from the Oncomine database, Breast cancer Gene-Expression Miner v4.5, TNMplot, MuTarget, PrognoScan database, and clinical bioinformatics to investigate PGK1 expression distribution and prognostic value in breast cancer patients. Our study revealed that the mRNA and protein expression levels of PGK1 were up-regulated in various clinicopathologic types of breast cancer. Moreover, the expression of PGK1 was correlated with mutations of common tumor suppressor genes TP53 and CDH1. In addition, we found that high mRNA level of PGK1 was significantly associated with poor OS, RFS, and DMFS. Notably, Cox regressionanalysis showed that PGK1 could be used as an independent prognostic marker. In summary, the aforementioned findings suggested that PGK1 might be not only explored as a potential biomarker, but also combined with TP53/CDH1 for chemotherapy in breast cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.


Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.


2007 ◽  
Vol 196 (3) ◽  
pp. 529-538 ◽  
Author(s):  
Zheng Zhao ◽  
Ichiro Sakata ◽  
Yusuke Okubo ◽  
Kanako Koike ◽  
Kenji Kangawa ◽  
...  

Ghrelin, an endogenous ligand for the GH secretagog receptor, is predominantly produced in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased after refeeding. It has also been reported that estrogen upregulates ghrelin expression and production and that somatostatin inhibits ghrelin secretion, whereas leptin has a paradoxical effect. Recently, several studies have shown that estrogen, somatostatin, and leptin are produced in the stomach, but the direct effects of these gastric hormones on ghrelin expression in a fasting state remain obscure. In this study, we examined the mRNA expression levels of gastric ghrelin, aromatase (estrogen synthetase), leptin and somatostatin, and concentrations of stomach leptin and portal vein 17β-estradiol in fasted male rats. After 48 h of fasting, although gastric ghrelin mRNA level was significantly increased, both gastric leptin mRNA level and leptin content were decreased. Further, refeeding of fasted rats resulted in a decrease in ghrelin expression level and an increase in leptin expression level. On the other hand, gastric estrogen and somatostatin levels did not change after fasting. In vitro studies revealed that leptin dose-dependently inhibited ghrelin expression and also inhibited estrogen-stimulated ghrelin expression. Moreover, ghrelin cells were found to be tightly surrounded by leptin cells. RT-PCR analysis clearly showed that long and short forms of the leptin receptor are expressed in the rat stomach. These results strongly suggest that an elevated gastric ghrelin expression level in a fasting state is regulated by attenuated restraint from decreased gastric leptin level.


Author(s):  
Xiaofei WU

Background: We aimed to investigate the expressions of miR-21 and miR-210 in the breast cancer tissue and their correlation with clinicopathological features and prognosis. Methods: A retrospective analysis was performed on 68 patients with breast cancer treated surgically in Wuhan General Hospital of Guangzhou Military in 2014-2015. The breast cancer tissue and the adjacent normal tissue were collected from the patients. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miR-21 and miR-210 in the breast cancer and adjacent normal tissues. Results: According to qRT-PCR, the expression levels of miR-210 and miR-21 in the breast cancer tissue were significantly higher than those in the adjacent normal tissue (P<0.05), which were significantly correlated with lymph node metastasis, clinical staging and differentiation of patients (P<0.05). miR-21 and miR-210 were significantly positive correlated in both breast cancer tissues and adjacent normal tissues (r=0.7014, 0.7502, P<0.001). The survival rate in the miR-210 high expression group was significantly lower than that in the miR210 low expression group (P<0.05), whereas there was no significant difference between the miR-21 high and low expression groups. Conclusion: miR-21 and miR-210 are highly expressed in the breast cancer tissue and significantly correlated with lymph node metastasis, clinical staging and differentiation. miR-210, the up-regulated expression of which is related to the poor prognosis of patients with breast cancer, may be a potential prognostic indicator for breast cancer, which can be used to judge the prognosis.


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