Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.

Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.

Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC. METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done. RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10). CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.

Photo-genosensor for Trichomonas vaginalis based on gold nanoparticles-genomic DNA.

Trichomoniasis, an infectious disease caused by a parasite called Trichomonas vaginalis (T. vaginalis), enhances the risk of HIV infection, cervical and prostate cancer, and infertility. Therefore, efforts have to be made for accurate, specific, and rapid diagnosise and treatment of trichomoniasis. Today, optical nanosensors have created an opportunity for diagnosis without sophisticated and expensive tools and the need for expertise; at the same time, they are highly sensitive and fast. An optical nano-genosensor was designed by conjugation of gold nanoparticles and a specific oligonucleotide (AuNPs-probe) from repeated DNA target for specific and sensitive polymerase chain reaction diagnosis of T. vaginalis gene sequence (L23861.1). The hybridization of AuNPs-probe was investigated with different concentrations of complementary sequence in synthesized target, gene sequence of standard T. vaginalis genomic DNA extraction, and PCR products of genomic DNA samples extracted from patients. Negative samples including synthesized non-complementary sequence, genomics DNA of other pathogens, and genomics DNA of healthy persons were considered for proof of the accuracy of the sensor function. The occurrence of correct hybridization was detected by adding acid to the medium and observing the changes in the color of the medium and spectroscopic spectrum. Based on spectrophotometric results, the fabricated genosensor had detection limits of 35.16 and 31 pg µL-1 for the detection of synthetic target and genomic DNA sequences, respectively. The results confirmed the correct function of genosensor for the detection of T. vaginalis in clinical samples. Advantages such as low cost, visual detection, speed, and easy diagnosis encourage the use of this sensor in pathogen detection in the future.