Tümör baskılayıcı gen CHFR'nin meme kanserinde susturulma mekanizmasının 3' UTR açısından irdelenmesi

TÜBİTAK SBAG Proje01.09.201

USP32 (ubiquitin specific peptidase 32)

Review on USP32 (ubiquitin specific peptidase 32), with data on DNA, on the protein encoded, and where the gene is implicated

Connections between CHFR, the cell cycle and chemosensitivity Are they critical in cancer?

Commentary to: Alternative efficacy-predicting markers for paclitaxel instead of CHFR in non-small cell lung cancer Masafumi Takeshita, Takaomi Koga, Koichi Takayama, Tokujiro Yano, Yoshihiko Maehara, Yoichi Nakanishi and Katsuo Sueish

HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1)

Heterogeneous nuclear ribonucleoprotein (HNRNPA1) gene maps to chromosome 12, plus strand and has 13 exons and 12 introns. There are three reported transcripts due to the alternative splicing. HNRNPA1 is one of the most abundant and ubiquitously expressed nuclear proteins. HNRNPA1 is a member of RNA-binding protein family comprising of 20 members in humans (Dreyfuss, 1993; Pinol-Roma, Choi, Matunis, & Dreyfuss, 1988). HNRNPA1 has diverse roles in RNA splicing, telomere length maintenance, miRNA maturation and mRNA transport from nucleus to cytoplasm

ALCAM (Activated Leukocyte Cell Adhesion Molecule)

ALCAM (Activated Leukocyte Cell Adhesion Molecule), also known as CD166 (cluster of differentiation 166), is a member of a subfamily of immunoglobulin receptors with five immunoglobulin-like domains (VVC2C2C2) in the extracellular domain

Nükleik asit tabanlı sandviç formatında mikroRNA dizi platformunun geliştirilmesi ve meme kanseri çalışmalarında kullanım potansiyelinin araştırılması

TÜBİTAK MAG01.09.201

CHFR (Checkpoint with fork-head associated and ring finger)

Growing evidence in mice, primary human tumors, and mammalian cell culture models indicate that CHFR may function as a potent tumor suppressor. CHFR functions as part of an early G2/M checkpoint, more specifically in antephase. Antephase refers to late G2 when chromosome condensation starts. This early mitotic checkpoint causes a delay in chromosome condensation in response to mitotic stresses. The human CHFR gene was originally identified during a search for novel cell cycle checkpoint proteins that have fork-head associated domains. Initial analysis indicated that the CHFR-associated G2/M checkpoint was inactivated in a subset of cancers as demonstrated by high mitotic indices (a high percentage of cells that have condensed chromosomes) in response to exposure to the microtubule poison, nocodazole, due to lack of CHFR expression or CHFR mutations in various cancers. Many other studies showed promoter hypermethylation leading to low/no expression of CHFR

Identification of an mRNA isoform switch for HNRNPA1 in breast cancers.

Roles of HNRNPA1 are beginning to emerge in cancers; however, mechanisms causing deregulation of HNRNPA1 function remain elusive. Here, we describe an isoform switch between the 3′-UTR isoforms of HNRNPA1 in breast cancers. We show that the dominantly expressed isoform in mammary tissue has a short half-life. In breast cancers, this isoform is downregulated in favor of a stable isoform. The stable isoform is expressed more in breast cancers, and more HNRNPA1 protein is synthesized from this isoform. High HNRNPA1 protein levels correlate with poor survival in patients. In support of this, silencing of HNRNPA1 causes a reversal in neoplastic phenotypes, including proliferation, clonogenic potential, migration, and invasion. In addition, silencing of HNRNPA1 results in the downregulation of microRNAs that map to intragenic regions. Among these miRNAs, miR-21 is known for its transcriptional upregulation in breast and numerous other cancers. Altogether, the cancer-specifc isoform switch we describe here for HNRNPA1 emphasizes the need to study gene expression at the isoform level in cancers to identify novel cases of oncogene activation

Could MicroRNAs be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview

Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with an annual incidence of <6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience and limited therapeutic options. There has been a growing interest in the field of microRNAs (miRNAs), a class of small non-coding RNAs of 22 nucleotides in length, because of their potential to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational repression by interacting with the 30 untranslated region (30-UTR) of target mRNAs, as well as other regions and gene promoters, as well as activating translation or regulating transcription under certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few studies have been performed on RGCs. In this review, we summarize the data currently available regarding RGCs.peer-reviewe

EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers

Epidermal growth factor receptor (EGFR) has critical roles in epithelial cell physiology. Over-expression and over-activation of EGFR have been implicated in diverse cancers, including triple-negative breast cancers (TNBCs), prompting anti-EGFR therapies. Therefore, developing potent therapies and addressing the inevitable drug resistance mechanisms necessitates deciphering of EGFR related networks. Here, we describe Sorting Nexin 3 (SNX3), a member of the recycling retromer complex, as a critical player in the epidermal growth factor (EGF) stimulated EGFR network in TNBCs. We show that SNX3 is an immediate and sustained target of EGF stimulation initially at the protein level and later at the transcriptional level, causing increased SNX3 abundance. Using a proximity labeling approach, we observed increased interaction of SNX3 and EGFR upon EGF stimulation. We also detected colocalization of SNX3 with early endosomes and endocytosed EGF. Moreover, we show that EGFR protein levels are sensitive to SNX3 loss. Transient RNAi models of SNX3 downregulation have a temporary reduction in EGFR levels. In contrast, long-term silencing forces cells to recover and overexpress EGFR mRNA and protein, resulting in increased proliferation, colony formation, migration, invasion in TNBC cells, and increased tumor growth and metastasis in syngeneic models. Consistent with these results, low SNX3 and high EGFR mRNA levels correlate with poor relapse-free survival in breast cancer patients. Overall, our results suggest that SNX3 is a critical player in the EGFR network in TNBCs with implications for other cancers dependent on EGFR activity.Chemical Immunolog