DNA Hypomethylation-Mediated Transcription Dysregulation Participates in Pathogenesis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggests that abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. Herein, a dehydroepiandrosterone-induced PCOS-like mouse model which has a similar metabolic and reproductive phenotype as human patients with PCOS was generated. It was used to experimentally validate the potential role of aberrant DNA methylation in PCOS in this study. Integrated DNA methylation and transcriptome analysis revealed the potential role of genomic DNA hypomethylation in transcription regulation of PCOS and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, i.p. injection of S-adenosylmethionine increased the overall DNA methylation level of PCOS-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in PCOS-like mice. These findings provide direct evidence showing the importance of normal DNA methylation in epigenetic regulation of PCOS and potential targets for diagnosis and treatment of the disease.

Prevalence of oral mucosal lesions in patients with systemic Lupus Erythematosus: a systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause a range of symptoms, including oral mucosal lesions (OMLs). The prevalence of OMLs in SLE patients and their associated factors have been studied in various regions, but the results are inconsistent. This study aims to evaluate the prevalence of OMLs in patients with SLE. METHODS: Observational studies of OML prevalence in SLE patients published before 2022 were retrieved from PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library without language restriction. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ). RESULTS: Our meta-analysis included 113 studies with a total of 53,307 SLE patients. We found that the prevalence of OMLs in SLE patients was 31% (95% CI: 28%, 35%), with oral ulcers being present in 30% of SLE patients (95% CI: 26%, 33%). Subgroup analysis showed that the prevalence of OMLs varied significantly by region, disease activity, and sample size (p ≤ 0.01). However, gender and year of publication had little effect on the prevalence of OMLs (p = 0.78 and 0.30, respectively). Oral ulcers were significantly associated with age of onset (p = 0.02), geographic location (p < 0.01), and race (p < 0.01). We also found that the prevalence of oral erythema was 9%, oral candidiasis was 9%, petechiae was 8%, cheilitis was 6%, and white plaque was 3%. CONCLUSIONS: Our analysis showed that the prevalence of OMLs varied significantly by region and disease activity, and child-onset patients of Indian, Malay, and Caucasian descent were more likely to have oral ulcers. The high prevalence of OML in SLE patients emphasizes the importance of regular oral examination and management in the comprehensive care of individuals with SLE.

Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex.

The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes.

Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations.

The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.

Leaf functional traits differentiation in relation to covering materials of urban tree pits.

BACKGROUND: Understanding the ecological strategies of urban trees to the urban environment is crucial to the selection and management of urban trees. However, it is still unclear whether urban tree pit cover will affect plant functional traits. Here, we study the response of urban trees to different tree pit covers, analyzed the effects of different cover types on soil properties and their trade-off strategies based on leaf functional traits. RESULTS: We found that there were obvious differences in the physical properties of the soil in different tree pit covers. Under the different tree pit cover types, soil bulk density and soil porosity reached the maximum under cement cover and turf cover, respectively. We found that tree pit cover significantly affected the leaf properties of urban trees. Leaf thickness, chlorophyll content index and stomatal density were mainly affected by soil bulk density and non-capillary porosity in a positive direction, and were affected by soil total porosity and capillary porosity in a negative direction. Leaf dry matter content and stomata area were mainly negatively affected by soil bulk density and non-capillary porosity, and positively affected by soil total porosity and capillary porosity. Covering materials of tree pits promoted the functional adjustment of plants and form the best combination of functions. CONCLUSION: Under the influence of tree pit cover, plant have low specific leaf area, stomata density, high leaf thickness, chlorophyll content index, leaf dry matter content, leaf tissue density and stomata area, which belong to "quick investment-return" type in the leaf economics spectrum.

Leaf reflectance and functional traits as environmental indicators of urban dust deposition.

BACKGROUND: How to quickly predict and evaluate urban dust deposition is the key to the control of urban atmospheric environment. Here, we focus on changes of plant reflectance and plant functional traits due to dust deposition, and develop a prediction model of dust deposition based on these traits. RESULTS: The results showed that (1) The average dust deposition per unit area of Ligustrum quihoui leaves was significantly different among urban environments (street (18.1001 g/m2), community (14.5597 g/m2) and park (9.7661 g/m2)). Among different urban environments, leaf reflectance curves tends to be consistent, but there were significant differences in leaf reflectance values (park (0.052-0.585) > community (0.028-0.477) > street (0.025-0.203)). (2) There were five major reflection peaks and five major absorption valleys. (3) The spectral reflectances before and after dust removal were significantly different (clean leaves > dust-stagnant leaves). 695 ~ 1400 nm was the sensitive range of spectral response. (4) Dust deposition has significant influence on slope and position of red edge. Red edge slope was park > community > street. After dust deposition, the red edge position has obviously "blue shift". The moving distance of the red edge position increases with the increase of dust deposition. The forecast model of dust deposition amount established by simple ratio index (y = 2.517x + 0.381, R2 = 0.787, RMSE (root-mean-square error) = 0.187. In the model, y refers to dust retention, x refers to simple ratio index.) has an average accuracy of 99.98%. (5) With the increase of dust deposition, the specific leaf area and chlorophyll content index decreased gradually. The leaf dry matter content, leaf tissue density and leaf thickness increased gradually. CONCLUSION: In the dust-polluted environment, L. quihoui generally presents a combination of characters with lower specific leaf area, chlorophyll content index, and higher leaf dry matter content, leaf tissue density and leaf thickness. Leaf reflectance spectroscopy and functional traits have been proved to be effective in evaluating the changes of urban dust deposition.

Metabolic interventions: A new insight into the cancer immunotherapy.

Metabolic reprogramming confers cancer cells plasticity and viability under harsh conditions. Such active alterations lead to cell metabolic dependency, which can be exploited as an attractive target in development of effective antitumor therapies. Similar to cancer cells, activated T cells also execute global metabolic reprogramming for their proliferation and effector functions when recruited to the tumor microenvironment (TME). However, the high metabolic activity of rapidly proliferating cancer cells can compete for nutrients with immune cells in the TME, and consequently, suppressing their anti-tumor functions. Thus, therapeutic strategies could aim to restore T cell metabolism and anti-tumor responses in the TME by targeting the metabolic dependence of cancer cells. In this review, we highlight current research progress on metabolic reprogramming and the interplay between cancer cells and immune cells. We also discuss potential therapeutic intervention strategies for targeting metabolic pathways to improve cancer immunotherapy efficacy.

TP53 loss creates therapeutic vulnerability in colorectal cancer.

TP53, a well-known tumour suppressor gene that encodes p53, is frequently inactivated by mutation or deletion in most human tumours. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment owing to the complexity of p53 signalling. Here we demonstrate that genomic deletion of TP53 frequently encompasses essential neighbouring genes, rendering cancer cells with hemizygous TP53 deletion vulnerable to further suppression of such genes. POLR2A is identified as such a gene that is almost always co-deleted with TP53 in human cancers. It encodes the largest and catalytic subunit of the RNA polymerase II complex, which is specifically inhibited by α-amanitin. Our analysis of The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases reveals that POLR2A expression levels are tightly correlated with its gene copy numbers in human colorectal cancer. Suppression of POLR2A with α-amanitin or small interfering RNAs selectively inhibits the proliferation, survival and tumorigenic potential of colorectal cancer cells with hemizygous TP53 loss in a p53-independent manner. Previous clinical applications of α-amanitin have been limited owing to its liver toxicity. However, we found that α-amanitin-based antibody-drug conjugates are highly effective therapeutic agents with reduced toxicity. Here we show that low doses of α-amanitin-conjugated anti-epithelial cell adhesion molecule (EpCAM) antibody lead to complete tumour regression in mouse models of human colorectal cancer with hemizygous deletion of POLR2A. We anticipate that inhibiting POLR2A will be a new therapeutic approach for human cancers containing such common genomic alterations.

PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway.

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2-specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

OBJECTIVE: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target. DESIGN: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases. RESULTS: FLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis. CONCLUSIONS: Based on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.

The ATM kinase induces microRNA biogenesis in the DNA damage response.

The DNA damage response involves a complex network of processes that detect and repair DNA damage. Here we show that miRNA biogenesis is globally induced upon DNA damage in an ATM-dependent manner. About one-fourth of miRNAs are significantly upregulated after DNA damage, while loss of ATM abolishes their induction. KH-type splicing regulatory protein (KSRP) is a key player that translates DNA damage signaling to miRNA biogenesis. The ATM kinase directly binds to and phosphorylates KSRP, leading to enhanced interaction between KSRP and pri-miRNAs and increased KSRP activity in miRNA processing. Mutations of the ATM phosphorylation sites of KSRP impaired its activity in regulating miRNAs. These findings reveal a mechanism by which DNA damage signaling is linked to miRNA biogenesis.

A Correlational Study on Cerebral Microbleeds and Carotid Atherosclerosis in Patients with Ischemic Stroke.

PURPOSE: This study aimed to investigate the correlation between cerebral microbleeds and carotid atherosclerosis in patients with ischemic stroke. SUBJECTS AND METHODS: Patients with ischemic stroke treated in a hospital in China from 2016 to 2017 were enrolled in the study. Based on the results from susceptibility-weighted imaging, the patients were divided into cerebral microbleed and noncerebral microbleed groups. The degree of carotid atherosclerosis was assessed with carotid intima-media thickness (CIMB) and Crouse score of carotid plaque. The details of patients' demographic information, cerebrovascular disease-related risk factors, carotid atherosclerosis indices, cerebral microbleed distribution, and grading were recorded, compared, and analyzed. RESULTS: Logistic regression analysis of the 198 patients showed that CIMB and Crouse score were significantly correlated with the occurrence of cerebral microbleeds. The CIMB thickening group (P = .03) and the plaque group (P = .01) were more susceptible to cerebral microbleeds. In the distribution of cerebral microbleed sites, Crouse scores were the highest in the mixed group and showed a statistically significant difference (P < .01). As the degree of carotid atherosclerosis increased, the average number of cerebral microbleeds also increased (P < .01). The receiver operating characteristic curve analysis of the carotid atherosclerosis indices showed a statistically significant difference. The CIMB value combined with the Crouse score was the best indicator (P < .01). CONCLUSION: In patients with ischemic stroke, cerebral microbleeds are closely related to carotid atherosclerosis. Active control of carotid atherosclerosis is important to prevent cerebral microbleeds in patients with ischemic stroke.

A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4 acetylation.

A prompt and efficient DNA damage response (DDR) eliminates the detrimental effects of DNA lesions in eukaryotic cells. Basic and preclinical studies suggest that the DDR is one of the primary anti-cancer barriers during tumorigenesis. The DDR involves a complex network of processes that detect and repair DNA damage, in which long non-coding RNAs (lncRNAs), a new class of regulatory RNAs, may play an important role. In the current study, we identified a novel lncRNA, lncRNA-JADE, that is induced after DNA damage in an ataxia-telangiectasia mutated (ATM)-dependent manner. LncRNA-JADE transcriptionally activates Jade1, a key component in the HBO1 (human acetylase binding to ORC1) histone acetylation complex. Consequently, lncRNA-JADE induces histone H4 acetylation in the DDR. Markedly higher levels of lncRNA-JADE were observed in human breast tumours in comparison with normal breast tissues. Knockdown of lncRNA-JADE significantly inhibited breast tumour growth in vivo. On the basis of these results, we propose that lncRNA-JADE is a key functional link that connects the DDR to histone H4 acetylation, and that dysregulation of lncRNA-JADE may contribute to breast tumorigenesis.

MALAT1 promoted invasiveness of gastric adenocarcinoma.

BACKGROUND: Gastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown. Recently, non-coding RNAs have been recognized to promote metastasis in various cancers, including gastric cancer. METHODS: We found that metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is upregulated in gastric cancer tissue compared to adjacent normal tissue, as determined by microarray and subsequent qRT-PCR, then investigated the impact of MALAT1 on apoptosis, cell proliferation, and the cell cycle to dissect the carcinogenesis of gastric cancer, and examined mechanisms of invasion and metastasis. Expression of MALAT1 and U6 was determined by SYBR qRT-PCR in nine-teen gastric cancer cell lines and fifty fresh samples of cancer tissue and adjacent tissues. Downregulation of MALAT1 was accomplished with two different siRNAs. Cell proliferation was determined after treatment with these siRNAs. FACS using PI/Annexin-V staining was carried out. To analyze the invasiveness, a scratch wound-healing assay and a Matrigel invasion assay were performed. Cancer related gene expression assay was done after transfection of siR- MALAT1. RESULTS: The expression of MALAT1 was significantly elevated in various gastric cancer cell lines and gastric cancer tissues compared to normal cell lines and tissues (p < 0.01). siR-MALAT1 significantly reduced viable AGS cell numbers and induced apoptosis (p < 0.05). Deep invasion of tumor (advanced T stages) was more common in the high MALAT1-level group (p = 0.039). siR-MALAT1 significantly decreased AGS cell invasiveness and migration. siR-MALAT1 reduced expression of snail and N-cadherin, and elevated E-cadherin. The Wnt/ß-catenin related genes were significantly decreased by transfection of siRNA MALAT1. MALAT1 is involved in gastric carcinogenesis via inhibition of apoptosis and promotes invasiveness via the epithelial-to-mesenchymal transition. CONCLUSIONS: In our study, we found that deregulation of MALAT1 could be involved in both tumorigenesis and invasiveness in gastric cancer cells.

Targeting tumor suppressor genes for cancer therapy.

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis.

OBJECTIVE: MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. DESIGN: We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. RESULTS: MiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=-0.44, p<0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037, respectively), and shorter metastasis-free survival (HR 6.51, 95% CI 1.97 to 21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (HR 4.12, 95% CI 1.1 to 15.41, p=0.0175). CONCLUSIONS: MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC.

CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer.

The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.

MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer.

Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situ hybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.

miRNA response to DNA damage.

Faithful transmission of genetic material in eukaryotic cells requires not only accurate DNA replication and chromosome distribution but also the ability to sense and repair spontaneous and induced DNA damage. To maintain genomic integrity, cells undergo a DNA damage response using a complex network of signaling pathways composed of coordinate sensors, transducers and effectors in cell cycle arrest, apoptosis and DNA repair. Emerging evidence has suggested that miRNAs play a crucial role in regulation of DNA damage response. In this review, we discuss the recent findings on how miRNAs interact with the canonical DNA damage response and how miRNA expression is regulated after DNA damage.