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Metastatic spread of the cancer is usually the consequence of the activation of signaling pathways that generate cell motility and tissue invasion. Metastasis involves the reorganization of cytoskeleton and cell shape for the swift movement of the cells through extracellular matrix. Previously, we have described the invasive and metastatic role played by one of the members (Toca-1) of CIP4 subfamily of F-BAR proteins. In the present study, we address the role of another member (FBP17) of same family in the invasion breast cancer cells. Here, we report that the formin-binding protein 17 (FBP17) is highly expressed at both mRNA and protein levels in breast cancer cells. The study showed the association of FBP17 with cytoskeletal actin regulatory proteins like dynamin and cortactin. To determine its role in extracellular matrix (ECM) degradation, we achieved stable knockdown of FBP17 in MDA-MB-231 cells. FBP17 knockdown cells showed a defect and were found to be compromised in the degradation of ECM indicating the role of FBP17 in the invasion of breast cancer cells. Our results suggest that FBP17 is highly expressed in breast cancer cells and facilitates the invasion of breast cancer cells.

miRNAs are fascinating molecular players for gene regulation as individual miRNA can control multiple targets and a single target can be regulated by multiple miRNAs. Loss of miRNA regulated gene expression is often reported to be implicated in various human diseases like diabetes and cancer. Recently, geneticists across the world started reporting single nucleotide polymorphism (SNPs) in seed sequences of miRNAs. Similarly, SNPs are also reported in various target sequences of these miRNAs. Both the scenarios lead to dysregulated gene expression which may result in the progression of diseases. In the present paper, we explore SNPs in various miRNAs and their target sequences reported in various human cancers as well as diabetes. Similarly, we also present evidence of these mutations in various other human diseases.

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Formin binding protein 17 (FBP17) belongs to Cdc-42 interacting protein 4 subfamily of F-BAR proteins. Recently, we had reported that FBP17 was overexpressed in invasive breast cancer cells and interacts with the actin regulatory proteins. We also reported that FBP17 promotes invadopodia formation and enhances extracellular matrix degradation. The current study determines FBP17 expression in invasive ductal carcinomas (IDCs) using breast cancer tissue microarrays (TMAs) (82 IDCs with variable receptor status and 8 Normal adjacent tissues) and its correlation with the clinicopathological features. Immunohistochemistry of human breast cancer TMAs showed the significant elevation in the levels of FBP17 in breast cancer tissues than the normal (p ≤ 0.0001). Interestingly, FBP17 had a higher expression in invasive molecular subtypes HER2 and TNBC (p ≤ 0.05). Similarly, tumors with lymph node positive status showed elevated FBP17 expression in HER2 and TNBC subtypes (p ≤ 0.05). Surprisingly, grade 3 tumors demonstrated higher FBP17 expression (p ≤ 0.01) indicating its role in poorly differentiated tumors. Together, the data demonstrates the overexpression of FBP17 in invasive and poorly differentiated tumors. Understanding the role of FBP17 in poor differentiation and invasion of tumors in molecular subtypes at various level might represent as a potential molecular target against the disease.