Ovarian aging: mechanisms and intervention strategies.

Ovarian reserve is essential for fertility and influences healthy aging in women. Advanced maternal age correlates with the progressive loss of both the quantity and quality of oocytes. The molecular mechanisms and various contributing factors underlying ovarian aging have been uncovered.

Culture conditions of mouse ESCs impact the tumor appearance in vivo.

Various culture conditions by small molecules have been explored to extend pluripotency of stem cells, but their impacts on cell fate in vivo remain elusive. We systematically compared the effects of various culture conditions on the pluripotency and cell fate in vivo of mouse embryonic stem cells (ESCs) by tetraploid embryo complementation assay. Conventional ESC cultures in serum/LIF-based condition produced complete ESC mice and also the survival to adulthood at the highest rates of all other chemical-based cultures.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need.

Reprogramming of ovarian aging epigenome by resveratrol.

Resveratrol is an antiaging, antioxidant, and anti-inflammatory natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects for improving aging ovarian function. However, the mechanisms underlying prolonged reproductive longevity remain elusive.

Up-regulation of Dsg2 confered stem cells with malignancy through wnt/β-catenin signaling pathway.

In the previous study, we originally developed cancer stem cells (CSCs) models from mouse induced pluripotent stem cells (miPSCs) by culturing miPSCs in the conditioned medium of cancer cell lines, which mimiced as carcinoma microenvironment. However, the molecular mechanism of conversion in detail remains to be uncovered. Microarray analysis of the CSCs models in this study revealed Dsg2, one of the members of the desmosomal cadherin family, was up-regulated when compared with the original miPSCs.

The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells.

Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs.

Mechanisms of resistance to estrogen receptor modulators in ER+/HER2- advanced breast cancer.

Endocrine therapy represents a mainstay adjuvant treatment of estrogen receptor-positive (ER+) breast cancer in clinical practice with an overall survival (OS) benefit. However, the emergence of resistance is inevitable over time and is present in one-third of the ER+ breast tumors. Several mechanisms of endocrine resistance in ER+/HER2- advanced breast cancers, through ERα itself, receptor tyrosine signaling, or cell cycle pathway, have been identified to be pivotal in endocrine therapy.

Telomere Maintenance-Associated PML Is a Potential Specific Therapeutic Target of Human Colorectal Cancer.

Telomere length maintenance is essential for cell proliferation, which is particularly prominent in cancer. We validate that the primary colorectal tumors exhibit heterogeneous telomere lengths but mostly (90%) short telomeres relative to normal tissues. Intriguingly, relatively short telomeres are associated with tumor malignancy as indicated by poorly differentiated state, and these tumors contain more cancer stem-like cells (CSLCs) identified by several commonly used markers CD44, EPHB2 or LGR5.

Zfhx3 is essential for progesterone/progesterone receptor signaling to drive ductal side-branching and alveologenesis in mouse mammary glands.

Progesterone (Pg)/progesterone receptor (PR) signaling drives mammary gland side-branching and alveologenesis, but the mechanisms through which Pg/PR signaling functions remain to be clarified. Using in vitro and in vivo models and histological and molecular analyses, we determined the role of Zfhx3 transcription factor in mammary gland development driven by Pg/PR signaling. Postnatal deletion of Zfhx3 in mouse mammary epithelial cells attenuated side-branching morphogenesis and alveologenesis.

ZNF121 interacts with ZBRK1 and BRCA1 to regulate their target genes in mammary epithelial cells.

The novel zinc finger protein 121 (ZNF121) has been demonstrated to physically and functionally associate with the MYC oncoprotein to regulate cell proliferation and likely breast cancer development. To further understand how ZNF121 functions in cell proliferation and carcinogenesis, we identified and characterized the interaction of ZNF121 with zinc finger and BRCA1-interacting protein with a KRAB domain 1 (ZBRK1), a breast and ovarian cancer susceptibility protein 1 (BRCA1)-interacting protein, using the yeast two-hybrid assay and other approaches. We also found that ZNF121 bound to BRCA1.

LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway.

The elucidation of molecular events that confer tamoxifen resistance to estrogen receptor α (ER) positive breast cancer is of major scientific and therapeutic importance. Here, we report that LEM4 overexpression renders ER+ breast cancer cells resistant to tamoxifen by activating the cyclin D-CDK4/6 axis and the ERα signaling. We show that LEM4 overexpression accelerates tumor growth.

Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and triggers the unfolded protein response (UPR). Failure to resolve ER stress leads to apoptotic cell death via a yet unclear mechanism. Here, we show that RNF183, a membrane-spanning RING finger protein, localizes to the ER and exhibits classic E3 ligase activities.

Zinc finger factor ZNF121 is a MYC-interacting protein functionally affecting MYC and cell proliferation in epithelial cells.

MYC is a potent oncoprotein that modulates multiple cellular processes including proliferation, apoptosis, differentiation, stemness, senescence, and migration. Functioning primarily as a transcriptional factor, MYC interacts with a large number of proteins, and identification and characterization of MYC-interacting proteins are important for understanding how MYC functions. In this study, we used different systems to demonstrate that a novel zinc finger transcription factor, ZNF121, physically interacted with MYC, and the interaction involved their N-terminal regions.

MicroRNA 100 sensitizes luminal A breast cancer cells to paclitaxel treatment in part by targeting mTOR.

Luminal A breast cancer usually responds to hormonal therapies but does not benefit from chemotherapies, including microtubule-targeted paclitaxel. MicroRNAs could play a role in mediating this differential response. In this study, we examined the role of micro RNA 100 (miR-100) in the sensitivity of breast cancer to paclitaxel treatment.

Somatic Mutation of the SNP rs11614913 and Its Association with Increased MIR 196A2 Expression in Breast Cancer.

Common genetic variants (single-nucleotide polymorphisms [SNPs]) in microRNA genes may alter their maturation or expression, resulting in varied functional consequences. Several studies have evaluated the association between the SNP rs11614913 and cancer risk in diverse populations and in a range of cancers, with contradictory outcomes. In this study, we examined 114 paired samples (tumor and normal tissues) from breast cancer patients to study the genotype distribution and somatic mutation of the SNP in MIR 196A2 (rs11614913 C-T).

Cross-sectional atom probe tomography sample preparation for improved analysis of fins on SOI.

Sample preparation for atom probe tomography of 3D semiconductor devices has proven to significantly affect field evaporation and the reliability of reconstructed data. A cross-sectional preparation method is applied to state-of-the-art Si finFET technology on SOI. This preparation approach advantageously provides a conductive path for voltage and heat, offers analysis of many fins within a single tip, and improves resolution across interfaces of particular interest.

MSX2 mediates entry of human pluripotent stem cells into mesendoderm by simultaneously suppressing SOX2 and activating NODAL signaling.

How BMP signaling integrates into and destabilizes the pluripotency circuitry of human pluripotent stem cells (hPSCs) to initiate differentiation into individual germ layers is a long-standing puzzle. Here we report muscle segment homeobox 2 (MSX2), a homeobox transcription factor of msh family, as a direct target gene of BMP signaling and a master mediator of hPSCs' differentiation to mesendoderm. Enforced expression of MSX2 suffices to abolish pluripotency and induce directed mesendoderm differentiation of hPSCs, while MSX2 depletion impairs mesendoderm induction.

Loss of Leucine Zipper Putative Tumor Suppressor 1 (LZTS1) Expression Contributes to Lymph Node Metastasis of Breast Invasive Micropapillary Carcinoma.

Breast invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer with a high potential of lymph node metastasis, aggressive clinical behavior, and poor disease-free or overall survival. Expression of leucine zipper putative tumor suppressor 1 (LZTS1) was frequently lost or reduced in breast cancer tissues. This study investigated the expression of LZTS1 protein in breast IMPC tissues using immunohistochemistry.

[Structure and biological functions of mammalian LEM-domain proteins].

During the process of open mitosis in higher eukaryotic cells, the nuclear envelope (NE) is disassembled and reassembled with highly organized and periodical dynamic morphological changes. Recent studies demonstrated that LEM-domain protein family mediates interactions among inner nuclear membrane, nuclear lamina protein and chromatin by interacting with barrier-to-autointegration-factor (BAF). The structure and function of the ternary complex formed by LEM-domain protein, nuclear lamina protein and BAF are dependent on each other.

Genetic analysis and preliminary function study of miR-423 in breast cancer.

Common genetic variants (single nucleotide polymorphisms SNPs) in microRNA (miRNA) genes may alter their maturation or expression and play a role in the formation of human cancer. Recently, the association between the SNP rs6505162 in pre-miR-423 and cancer risk has been frequently evaluated in diverse populations and in a range of cancers. In this study, we determined the genotypes of SNP rs6505162 in 5 matched cell lines (breast cancer cell lines and their corresponding peripheral blood cell lines) and 114 matched clinical specimens (clinical breast carcinoma specimens and their corresponding normal tissues), compared the processing efficiency of pri-miRNA to mature forms between pre-miR-423-12C (wild-type) and pre-miR-423-12A (mutant-type) expression vectors, and evaluated the function of miR-423 on cell proliferation.

Frequent mutation of rs13281615 and its association with PVT1 expression and cell proliferation in breast cancer.

The q24 band of chromosome 8 (8q24) is frequently amplified in human cancers including breast cancer, and several SNPs (single nucleotide polymorphisms) at 8q24, including rs13281615, have been identified for their association with cancer risks. These SNPs are in a "gene desert" region, and their functions in cancer development remain to be illustrated, although several of the SNPs appear to influence the genes in the "desert" in a long-range manner, including the v-myc avian myelocytomatosis viral oncogene homolog (MYC) and the non-protein coding plasmacytoma variant translocation 1 (PVT1), both of which have been implicated in human cancers. In the current study, we examined rs13281615 for its potential role in breast cancer using normal and cancer tissues from 121 Chinese women with breast cancer.

KLF5 activates microRNA 200 transcription to maintain epithelial characteristics and prevent induced epithelial-mesenchymal transition in epithelial cells.

KLF5 is an essential basic transcriptional factor that regulates a number of physiopathological processes. In this study, we tested whether and how KLF5 modulates the epithelial-mesenchymal transition (EMT). Using transforming growth factor β (TGF-β)- and epidermal growth factor (EGF)-treated epithelial cells as an established model of EMT, we found that KLF5 was downregulated during EMT and that knockdown of KLF5 induced EMT even in the absence of TGF-β and EGF treatment, as indicated by phenotypic and molecular EMT properties.

ROOT HAIR DEFECTIVE3 family of dynamin-like GTPases mediates homotypic endoplasmic reticulum fusion and is essential for Arabidopsis development.

In all eukaryotic cells, the endoplasmic reticulum (ER) forms a tubular network whose generation requires the fusion of ER membranes. In Arabidopsis (Arabidopsis thaliana), the membrane-bound GTPase ROOT HAIR DEFECTIVE3 (RHD3) is a potential candidate to mediate ER fusion. In addition, Arabidopsis has two tissue-specific isoforms of RHD3, namely RHD3-like (RL) proteins, and their function is not clear.