ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway.

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

K48-linked deubiquitination of VGLL4 by USP15 enhances the efficacy of tumor immunotherapy in triple-negative breast cancer.

Immunotherapy based on PD-1/PD-L1 antagonists has been demonstrated to be efficacious in inducing tumor remission in patients with triple-negative breast cancer (TNBC). However, tumor immune evasion caused by the PD-1/PD-L1 pathway inhibits the immunotherapeutic effect of PD-1/PD-L1 inhibitors against TNBC. Therefore, identifying potential targets for blocking the PD-1/PD-L1 pathway is a compelling strategy for TNBC treatment. Here, we discovered that VGLL4 could inhibit PD-L1 transcription by suppressing STAT3 activation, thereby enhancing the efficacy of anti-PD-1 antibody immunotherapy in TNBC. Low expression of USP15, a deubiquitinating enzyme of VGLL4, was associated with reduced CD8+ T cell infiltration and poor prognosis in TNBC patients. USP15 was found to inhibit PD-L1 transcription, leading to increased CD8+ T cell infiltration and thus enhancing the efficacy of TNBC immunotherapy. Furthermore, SART3 regulated VGLL4 stability and PD-L1 transcription by influencing the nuclear translocation of USP15. In conclusion, our study provides new insights into the biological regulation of PD-L1, identifies a previously unrecognized regulator of this critical immune checkpoint, and highlights potential therapeutic targets for overcoming immune evasion in TNBC.

LINC01572 promotes triple-negative breast cancer progression through EIF4A3-mediated ß-catenin mRNA nuclear exportation.

Long noncoding RNAs have been reported to be involved in the development of breast cancer. LINC01572 was previously reported to promote the development of various tumors. However, the potential biological function of LINC01572 in breast cancer remains largely unknown. R language was used to perform bioinformatic analysis of The Cancer Genome Atlas data. The expression level of RNAs was examined by RT-qPCR. The effect of knocking down or overexpression LINC01572 in triple-negative breast cancer (TNBC) cell lines was evaluated by detecting cell proliferation, migrant action. RNA immunoprecipitation assay and RNA pull-down assay were performed to explore the regulatory relationship between LINC01572, EIF4A3, and ß-catenin. Bioinformatics analysis identifies LINC01572 as an oncogene of breast cancer. LINC01572 is over-expressed in TNBC tissues and cell lines, correlated with poor clinical prognosis in BC patients. Cell function studies confirmed that LINC01572 facilitated the proliferation and migration of TNBC cells in both vivo and vitro. Mechanistically, ß-catenin mRNA and EIF4A3 combine spatially to form a complex, LINC01572 helps transport this complex from the nucleus to the cytoplasm, thereby facilitating the translation of ß-catenin. Our findings confirm that LINC01572 acts as a tumor promoter and may act as a biomarker in TNBC. In addition, novel molecular regulatory relationships involving LINC01572/EIF4A3/ß-catenin are critical to the development of TNBC, which led to a new understanding of the mechanisms of TNBC progression and shows a new target for precision treatment for TNBC.

Real-Time Evaluation of Helicobacter pylori Infection by Convolution Neural Network During White-Light Endoscopy: A Prospective, Multicenter Study (With Video).

INTRODUCTION: Convolutional neural network during endoscopy may facilitate evaluation of Helicobacter pylori infection without obtaining gastric biopsies. The aim of the study was to evaluate the diagnosis accuracy of a computer-aided decision support system for H. pylori infection (CADSS-HP) based on convolutional neural network under white-light endoscopy. METHODS: Archived video recordings of upper endoscopy with white-light examinations performed at Sir Run Run Shaw Hospital (January 2019-September 2020) were used to develop CADSS-HP. Patients receiving endoscopy were prospectively enrolled (August 2021-August 2022) from 3 centers to calculate the diagnostic property. Accuracy of CADSS-HP for H. pylori infection was also compared with endoscopic impression, urea breath test (URT), and histopathology. H. pylori infection was defined by positive test on histopathology and/or URT. RESULTS: Video recordings of 599 patients who received endoscopy were used to develop CADSS-HP. Subsequently, 456 patients participated in the prospective evaluation including 189 (41.4%) with H. pylori infection. With a threshold of 0.5, CADSS-HP achieved an area under the curve of 0.95 (95% confidence interval [CI], 0.93-0.97) with sensitivity and specificity of 91.5% (95% CI 86.4%-94.9%) and 88.8% (95% CI 84.2%-92.2%), respectively. CADSS-HP demonstrated higher sensitivity (91.5% vs 78.3%; mean difference = 13.2%, 95% CI 5.7%-20.7%) and accuracy (89.9% vs 83.8%, mean difference = 6.1%, 95% CI 1.6%-10.7%) compared with endoscopic diagnosis by endoscopists. Sensitivity of CADSS-HP in diagnosing H. pylori was comparable with URT (91.5% vs 95.2%; mean difference = 3.7%, 95% CI -1.8% to 9.4%), better than histopathology (91.5% vs 82.0%; mean difference = 9.5%, 95% CI 2.3%-16.8%). DISCUSSION: CADSS-HP achieved high sensitivity in the diagnosis of H. pylori infection in the real-time test, outperforming endoscopic diagnosis by endoscopists and comparable with URT. Clinicaltrials.gov ; ChiCTR2000030724.

miR-186-ANXA9 signaling inhibits tumorigenesis in breast cancer.

Breast cancer (BC) ranks as the highest incidence among cancer types in women all over the world. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNA in cells mostly functioning to silence the target mRNAs. In the current study, a miRNA screening analysis identified miR-186-5p to be downregulated in human breast cancer tumors. Functional studies in vitro demonstrated that overexpression of miR-186-5p inhibited cellular proliferation and induced cell apoptosis in multiple breast cancer cell lines including MDA-MB-231, MCF-7, and BT549 cells. Transplantation of the miR-186-5p-overexpressing MDA-MB-231 cells into nude mice significantly inhibited mammary tumor growth in vivo. Sequence blast analysis predicted annexin A9 (ANXA9) as a target gene of miR-186-5p, which was validated by luciferase reporter assay, QRT-PCR analysis, and western blot. Additional gene expression analysis of clinical tumor samples indicated a negative correlation between miR-186-5p and ANXA9 in human breast cancer. Knockdown of ANXA9 mimicked the phenotype of miR-186-5p overexpression. Reintroduction of ANXA9 back rescued the miR-186-5p-induced cell apoptosis. In addition, miR-186-5p decreased the expression of Bcl-2 and increased the expression of p53, suggesting a mechanism regulating miR-186-5p-induced cellular apoptosis. In summary, our study is the first to demonstrate miR-186-5p-ANXA9 signaling in suppressing human breast cancer. It provided a potential therapeutic target in breast cancer.

Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker.

Background: The liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect of SPARCL1 on BC. Methods: The publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein-protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1 expression in BC tissues and cell lines was verified by RT-qPCR. Further in vitro experiments were performed to investigate the biological functions of SPARCL1 in BC cells. Results: We identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis of SPARCL1 revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels of SPARCL1 were detected in BC tissues compared to adjacent tissues. The in vitro experiments showed that SPARCL1 knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression of SPARCL1. Conclusion: We identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.

CircRNF10-DHX15 interaction suppressed breast cancer progression by antagonizing DHX15-NF-κB p65 positive feedback loop.

BACKGROUND: Breast cancer (BC) is a common threat to women. The continuous activation of nuclear factor kappa B (NF-κB) signaling pathway contributes to the development of BC. This study aimed to investigate the role of a circular RNA (circRNF10) in BC progression and regulating NF-κB signaling pathway. METHODS: Bioinformatics analysis, RT-qPCR, subcellular fractionation, FISH, RNase R treatment, and actinomycin D assay were used to explore the expression and characteristics of circRNF10 in BC. The biological functions of circRNF10 in BC were analyzed by MTT assay, colony formation assay, wound healing assay, and Transwell assay. RNA pulldown and RIP assay were used to identify the interaction between circRNF10 and DEAH (Asp-Glu-Ala-His) box helicase 15 (DHX15). The impact of circRNF10-DHX15 interaction on NF-κB signaling pathway was explored by western blot, IF, and co-IP. Furthermore, dual-luciferase reporter assay, ChIP, and EMSA were performed to assess the effect of NF-κB p65 on DHX15 transcription. RESULTS: CircRNF10 was downregulated in BC, and lower expression of circRNF10 was related to poor prognosis of patients with BC. CircRNF10 inhibited the proliferation and migration of BC. Mechanically, circRNF10-DHX15 interaction sequestered DHX15 from NF-κB p65, thereby inhibiting the activation of NF-κB signaling pathway. On the other hand, NF-κB p65 enhanced DHX15 transcription by binding to the promoter of DHX15. Altogether, circRNF10 impaired the DHX15-NF-κB p65 positive feedback loop and suppressed the progression of BC. CONCLUSION: CircRNF10-DHX15 interaction suppressed the DHX15-NF-κB p65 positive feedback loop, thereby inhibiting BC progression. These findings provide new insights in the continuous activation of NF-κB signaling pathway and raised potential therapeutic approach for BC treatment.

DNMT3a-dermatopontin axis suppresses breast cancer malignancy via inactivating YAP.

Breast cancer (BC) is the most common malignant tumor in women worldwide, and its recurrence and metastasis negatively affect patient prognosis. However, the mechanisms underlying its tumorigenesis and progression remain unclear. Recently, the influence of dermatopontin (DPT), which is an extracellular matrix protein, has been proposed in the development of cancer. Here we found that DNMT3a-mediated DPT, promoter hypermethylation results in the downregulation of DPT expression in breast cancer and its low expression correlated with poor prognosis. Notably, DPT directly interacted with YAP to promote YAP Ser127 phosphorylation, and restricted the translocation of endogenous YAP from the cytoplasm to the nucleus, thereby suppressing malignant phenotypes in BC cells. In addition, Ectopic YAP overexpression reversed the inhibitory effects of DPT on BC growth and metastasis. Our study showed the critical role of DPT in regulating BC progression, making it easier to explore the clinical potential of modulating DPT/YAP activity in BC targeted therapies.

SHP2 inhibition mitigates adaptive resistance to MEK inhibitors in KRAS-mutant gastric cancer through the suppression of KSR1 activity.

Despite the promising antitumor activity of RAF/MEK inhibitors for RAS-driven cancers, not all patients respond to these therapies. Adaptive resistance has been reported as a major culprit in non-responders, which can be reversed by SHP2 inhibitors (SHP2is) in multiple cancer cells; however, the underlying mechanisms remain unknown. In this study, we found that KRAS-mutant gastric cancer cells respond to MEK inhibitors (MEKis) with adaptive resistance. Markedly, SHP2 activation accompanied by ERK signaling restoration in MEKi-treated cells, and a MEKi and SHP2i combination had a synergistic effect on downstream signaling blockade. In vivo, SHP099 combined with AZD6244 (selumetinib) was highly efficacious for the treatment of xenografts. Mechanistically, SHP2 was found to interact with the scaffold protein KSR1 through its protein tyrosine phosphatase domain. KSR1 knockdown sensitized cells to AZD6244, whereas a KSR1 activating mutation (S269A) diminished the synergistic anti-proliferative effect of SHP2i and MEKi. Interestingly, activated SHP2, during adaptive resistance to MEKis, impaired the interaction with KSR1, activating KSR1 to promote MAPK signaling. In conclusion, SHP2 promotes adaptive resistance to MEKis by activating KSR1; selumetinib combined with SHP099 might be an available therapeutic strategy for KRAS-mutant gastric cancers.

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of discovering safe and effective agents for a given disease. Since the outbreak of COVID-19 pandemic, drug repurposing strategy has been widely used to discover potential antiviral agents, and some of these drugs have advanced into clinical trials. Antitumor drugs compromise a vast variety of compounds and exhibit extensive mechanism of action, showing promising properties in drug repurposing. In this review, we revisit the potential value of antitumor drugs in the treatment of COVID-19 and systematically discuss their possible underlying mechanisms of the antiviral actions.

An end-to-end tracking method for polyp detectors in colonoscopy videos.

Deep learning based computer-aided diagnosis technology demonstrates an encouraging performance in aspect of polyp lesion detection on reducing the miss rate of polyps during colonoscopies. However, to date, few studies have been conducted for tracking polyps that have been detected in colonoscopy videos, which is an essential and intuitive issue in clinical intelligent video analysis task (e.g. lesion counting, lesion retrieval, report generation). In the paradigm of conventional tracking-by-detection system, detection task for lesion localization is separated from the tracking task for cropped lesions re-identification. In the multi object tracking problem, each target is supposed to be tracked by invoking a tracker after the detector, which introduces multiple inferences and leads to external resource and time consumption. To tackle these problems, we proposed a plug-in module named instance tracking head (ITH) for synchronous polyp detection and tracking, which can be simply inserted into object detection frameworks. It embeds a feature-based polyp tracking procedure into the detector frameworks to achieve multi-task model training. ITH and detection head share the model backbone for low level feature extraction, and then low level feature flows into the separate branches for task-driven model training. For feature maps from the same receptive field, the region of interest head assigns these features to the detection head and the ITH, respectively, and outputs the object category, bounding box coordinates, and instance feature embedding simultaneously for each specific polyp target. We also proposed a method based on similarity metric learning. The method makes full use of the prior boxes in the object detector to provide richer and denser instance training pairs, to improve the performance of the model evaluation on the tracking task. Compared with advanced tracking-by-detection paradigm methods, detectors with proposed ITH can obtain comparative tracking performance but approximate 30% faster speed. Optimized model based on Scaled-YOLOv4 detector with ITH illustrates good trade-off between detection (mAP 91.70%) and tracking (MOTA 92.50% and Rank-1 Acc 88.31%) task at the frame rate of 66 FPS. The proposed structure demonstrates the potential to aid clinicians in real-time detection with online tracking or offline retargeting of polyp instances during colonoscopies.

The role of drug-metabolizing enzymes in synthetic lethality of cancer.

Drug-metabolizing enzymes (DMEs) have shown increasing importance in anticancer therapy. It is not only due to their effect on activation or deactivation of anticancer drugs, but also because of their extensive connections with pathological and biochemistry changes during tumorigenesis. Meanwhile, it has become more accessible to discovery anticancer drugs that selectively targeted cancer cells with the development of synthetic lethal screen technology. Synthetic lethal strategy makes use of unique genetic markers that different cancer cells from normal tissues to discovery anticancer agents. Dysregulation of DMEs has been found in various cancers, making them promising candidates for synthetic lethal strategy. In this review, we will systematically discuss about the role of DMEs in tumor progression, the application of synthetic lethality strategy in drug discovery, and a link between DMEs and synthetic lethal of cancer.

Circular RNA_0006014 promotes breast cancer progression through sponging miR-885-3p to regulate NTRK2 and PIK3/AKT pathway.

Breast cancer is the most common cancer in women worldwide. Numerous reports have demonstrated that circRNAs play an essential role in regulating the biological characteristics of breast cancer. However, there are currently no reports regarding the role of hsa_circ_0006014 in breast cancer. In this study, qRT-PCR was used to detect the expression of hsa_circ_0006014 and related genes. MTT, colony formation and Transwell assays were used to explore the potential biological functions of hsa_circ_0006014 in breast cancer cells. Western blotting was used to explore the potential molecular mechanisms involving hsa_circ_0006014. In vivo experiments were used to evaluate the influence of hsa_circ_0006014 on animal tumors. In this study, we found higher expression of hsa_circ_0006014 in breast tumor samples than in matched adjacent normal samples, and its expression was positively correlated with histological grade (grade iii). Phenotypically, hsa_circ_0006014 promoted the proliferation of MDA-MB-231 and MCF-7 breast cancer cells. Mechanistically, there were confirmed binding sites between hsa_circ_0006014 and miR-885-3p, and hsa_circ_0006014 promoted breast cancer cell proliferation partially by sponging miR-885-3p and influenced CDK2/CCNE1 and CDK4/6/CCND1. Furthermore, we found that hsa_circ_0006014 regulated NTRK2 through miR-885-3p to modulate the PIK3/AKT signaling pathway. Our results demonstrated that hsa_circ_0006014 promotes breast cancer progression by sponging miR-885-3p to regulate the NTRK2/PIK3CA/AKT axis.

Tumor-Derived circRNAs as Circulating Biomarkers for Breast Cancer.

Early diagnosis is the key to improving the prognosis of breast cancer (BC) patients; however, there are currently no circulating biomarkers that demonstrate good sensitivity and specificity. This study applied circular RNA (circRNA) microarray analysis, screening, and verification in BC plasma samples to identify three tumor-derived differentially expressed circRNAs: hsa_circ_0000091, hsa_circ_0067772, and hsa_circ_0000512. We constructed a diagnostic model using logistic regression analysis in the training set and established an optimal diagnostic model based on the three circRNAs, which showed sensitivity, specificity, and area under the curve (AUC) values of .971, .902, and .974, respectively. We then verified the diagnostic model in the test set which showed satisfactory stability for BC diagnosis. Additionally, the expression of hsa_circ_0000091 in plasma correlated with axillary lymph node (ALN) metastasis, TNM stage, and prognosis of BC patients. Furthermore, hsa_circ_0000091 combined with ultrasound showed predictive ability for ALN metastasis, with an AUC of .808. These findings suggested that the three identified circRNAs can be used as circulating biomarkers for BC diagnosis, with hsa_circ_0000091 potentially representing a prognostic biomarker for BC and novel approach for predicting ALN metastasis.

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis.

Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3'-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.

Simultaneous Recognition of Atrophic Gastritis and Intestinal Metaplasia on White Light Endoscopic Images Based on Convolutional Neural Networks: A Multicenter Study.

INTRODUCTION: Patients with atrophic gastritis (AG) or gastric intestinal metaplasia (GIM) have elevated risk of gastric adenocarcinoma. Endoscopic screening and surveillance have been implemented in high incidence countries. The study aimed to evaluate the accuracy of a deep convolutional neural network (CNN) for simultaneous recognition of AG and GIM. METHODS: Archived endoscopic white light images with corresponding gastric biopsies were collected from 14 hospitals located in different regions of China. Corresponding images by anatomic sites containing AG, GIM, and chronic non-AG were categorized using pathology reports. The participants were randomly assigned (8:1:1) to the training cohort for developing the CNN model (TResNet), the validation cohort for fine-tuning, and the test cohort for evaluating the diagnostic accuracy. The area under the curve (AUC), sensitivity, specificity, and accuracy with 95% confidence interval (CI) were calculated. RESULTS: A total of 7,037 endoscopic images from 2,741 participants were used to develop the CNN for recognition of AG and/or GIM. The AUC for recognizing AG was 0.98 (95% CI 0.97-0.99) with sensitivity, specificity, and accuracy of 96.2% (95% CI 94.2%-97.6%), 96.4% (95% CI 94.8%-97.9%), and 96.4% (95% CI 94.4%-97.8%), respectively. The AUC for recognizing GIM was 0.99 (95% CI 0.98-1.00) with sensitivity, specificity, and accuracy of 97.9% (95% CI 96.2%-98.9%), 97.5% (95% CI 95.8%-98.6%), and 97.6% (95% CI 95.8%-98.6%), respectively. DISCUSSION: CNN using endoscopic white light images achieved high diagnostic accuracy in recognizing AG and GIM.

MIR22HG inhibits breast cancer progression by stabilizing LATS2 tumor suppressor.

The long noncoding RNA called MIR22 host gene (MIR22HG) was previously identified as a tumor suppressor in several cancers. However, the biological function of MIR22HG in breast cancer remains unknown. In this study, we aimed to determine the function and molecular mechanism of MIR22HG in breast cancer progression using transcriptomics and biotechnological techniques. Our results showed that MIR22HG expression was lower in the cancerous tissues than in the paired adjacent normal breast tissues. Additionally, MIR22HG was found to be mainly located in the cytoplasm and acted as a miR-629-5p sponge. Notably, MIR22HG stabilized the expression of large tumor suppressor 2 (LATS2), which promoted the LATS2-dependent phosphorylation of YAP1 and suppressed the expression of its downstream target oncogenes, thereby inhibiting the proliferation and migration of breast cancer cells. Therefore, our findings reveal the MIR22HG-dependent inhibition of breast cancer cell proliferation and migration via the miR-629-5p/LATS2 pathway, providing new insights and identifying novel therapeutic targets for breast cancer treatment.

KIF23 promotes triple negative breast cancer through activating epithelial-mesenchymal transition.

BACKGROUND: KIF23 is a member of kinesin family, recent researches indicate KIF23 plays an important role in the proliferation and migration of malignant cancer cells. While the function and specific molecule mechanism of KIF23 in triple negative breast cancer remains unclear. METHODS: QRT-PCR and immunohistochemistry were conducted to analyze expression of KIF23 in triple negative breast cancer tissues and paired paracancer tissues. CCK-8 assay, colony formation assay, wound healing assay and transwell assay were applied for exploring phenotype changing of triple negative breast cancer cell lines MDA-MB-231 and BT549 after siRNA-induced knockdown of KIF23. Several bioinformatic databases were used for predicting miRNAs that combing with KIF23 mRNA and verified by dual luciferase reporter assay. Western blot assay was performed to explore downstream signaling pathway of KIF23. RESULTS: KIF23 was overexpressed in triple negative breast cancer, knockdown of KIF23 by siRNA inhibited proliferation and migration of TNBC cell lines MDA-MB-231 and BT549. Mechanistically, knockdown of KIF23 resulted in the suppression of Epithelial-Mesenchymal Transition. Meanwhile, miR-195-5p was downregulated in TNBC, and dual luciferase reporter assay indicated miR-195-5p could combine with 3'UTR of KIF23 thus promoting degradation of KIF23. CONCLUSIONS: KIF23 is a potential oncogene in triple negative breast cancer, miR-195-5p could combine with 3'UTR of KIF23. Our study reveals a new sight into triple negative breast cancer.

The Role of miR-640: A Potential Suppressor in Breast Cancer via Wnt7b/ß-catenin Signaling Pathway.

In this study, we demonstrated that miR-640 is significantly downregulated in breast cancer (BC) tissues and cell lines. Overexpression of miR-640 inhibited the proliferation and migration of BC in vitro and in vivo, while depletion of miR-640 exhibited the opposite effect. Importantly, miR-640 could directly target Wnt7b, thereby regulating Wnt/ß-catenin signaling pathway in BC. In conclusion, miR-640/Wnt7b suppresses BC cells tumorigenesis via Wnt/ß-catenin signaling pathway, which might be novel targets for BC targeted therapy.