Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.

METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2-breast cancer.

BACKGROUND: Chemotherapy is an important strategy for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+HER2-) breast cancer (BC), but this subtype has a low response rate to chemotherapy. Growing evidence indicates that N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells and that methyltransferase-like 3 (METTL3) participates in tumour progression in several cancer types. Therefore, exploring the function of METTL3 in HR+HER2- BC initiation and development is still important. METHODS: mRNA and protein expression levels were analysed by quantitative real-time polymerase chain reaction and western blotting, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. Cell cycle progression was assessed by flow cytometry. Cell migration and invasion were analysed by wound healing assays and transwell assays, respectively, and apoptosis was analysed by TUNEL assays. Finally, m6A modification was analysed by methylated RNA immunoprecipitation. RESULTS: Chemotherapy-induced downregulation of the m6A modification is regulated by METTL3 depletion in HR+HER2- BC. METTL3 knockdown in MCF-7/T47D cells decreased the drug sensitivity of HR+HER2- BC cells by promoting tumour proliferation and migration and inhibiting apoptosis. Mechanistically, CDKN1A is a downstream target of METTL3 that activates the AKT pathway and promotes epithelial-mesenchymal transformation (EMT). Moreover, a decrease in BAX expression was observed when m6A modification was inhibited with METTL3 knockdown, and apoptosis was inhibited by the reduction of caspase-3/-9/-8. CONCLUSION: METTL3 depletion promotes the proliferation and migration and decreases the drug sensitivity of HR+HER2- BC via regulation of the CDKN1A/EMT and m6A-BAX/caspase-9/-3/-8 signalling pathways, which suggests METTL3 played a tumour-suppressor role and it could be a potential biomarker for predicting the prognosis of patients with HR+HER2- BC.

Highly precise timing alignment of multi-wavelength interleaved cavity-less pulse sources with FROG.

Strictly uniform time interval between adjacent channels is a crucial requirement for the multi-wavelength interleaved (MWI) pulse sources, which difficult alignment can be easily solved by what we believe to be our novel method based on frequency-resolved optical gating (FROG). By utilizing highly precise measurements from FROG, which provide fully two-dimensional information of the pulses in time and frequency domain, we can intuitively identify the time mismatches between different channels in the MWI pulse sources. This enables us to directly align the timing of each channel with sub-picosecond resolution at the first time. MWI pulse sources with total repetition rate of 20.8 GHz (four wavelengths) and 41.6 GHz (eight wavelengths) are precisely aligned by the proposed method, this achievement will pave the way for advancements in photonic analog-digital converters (PADC), high-speed optical communications and so on.

Deep learning-based multifeature integration robustly predicts central lymph node metastasis in papillary thyroid cancer.

BACKGROUND: Few highly accurate tests can diagnose central lymph node metastasis (CLNM) of papillary thyroid cancer (PTC). Genetic sequencing of tumor tissue has allowed the targeting of certain genetic variants for personalized cancer therapy development. METHODS: This study included 488 patients diagnosed with PTC by ultrasound-guided fine-needle aspiration biopsy, collected clinicopathological data, analyzed the correlation between CLNM and clinicopathological features using univariate analysis and binary logistic regression, and constructed prediction models. RESULTS: Binary logistic regression analysis showed that age, maximum diameter of thyroid nodules, capsular invasion, and BRAF V600E gene mutation were independent risk factors for CLNM, and statistically significant indicators were included to construct a nomogram prediction model, which had an area under the curve (AUC) of 0.778. A convolutional neural network (CNN) prediction model built with an artificial intelligence (AI) deep learning algorithm achieved AUCs of 0.89 in the training set and 0.78 in the test set, which indicated a high prediction efficacy for CLNM. In addition, the prediction models were validated in the subclinical metastasis and clinical metastasis groups with high sensitivity and specificity, suggesting the broad applicability of the models. Furthermore, CNN prediction models were constructed for patients with nodule diameters less than 1 cm. The AUCs in the training set and test set were 0.87 and 0.76, respectively, indicating high prediction efficacy. CONCLUSIONS: The deep learning-based multifeature integration prediction model provides a reference for the clinical diagnosis and treatment of PTC.

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer.

Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper. Video Abstract.

RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

Prognosis Comparison Between Nipple-Sparing Mastectomy and Total Mastectomy in Breast Cancer: A Case-Control Study After Propensity Score Matching.

BACKGROUND: Currently, the operation rate of nipple-sparing mastectomy (NSM) is increasing. However, the long-term prognosis of NSM is not well documented. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term prognosis of NSM compared with total mastectomy (TM). METHODS: Population-level data of female breast cancer patients treated with NSM and TM were extracted from 1998 to 2016 from the SEER database. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables in comparisons. Kaplan-Meier analysis, log-rank test, and Cox proportional hazard regression were performed. RESULTS: A total of 5765 patients underwent NSM, which increased from 266 in 2004-2009 to 5370 in 2010-2016. A total of 134,528 patients underwent TM, and the number of patients undergoing TM continued to decline. The overall survival (OS) and breast cancer-specific survival (BCSS) were similar between the NSM group and the TM group (P = 0.058 and 0.87, respectively). For OS, subgroup analysis showed that patients with age ≥ 46, White race, median household income ≥ $70,000, hormone receptor-positive, and HER2 negative had a better prognosis for treatment with NSM. There was no significant difference in BCSS between the NSM group and the TM group. CONCLUSIONS: In recent years, the clinical application of NSM has been increasing. NSM is a proper procedure for breast cancer patients to achieve long-term survival.

A novel binding-induced DNAzyme motor triggered by survivin mRNA.

The accurate and sensitive detection of survivin mRNA is of great significance for cancer diagnosis and treatment. However, limited by the low-abundance mRNA in live cells, most strategies of survivin mRNA detection that were one-to-one signal-triggered model (one target triggered one signal) were inapplicable in practice. Here, we reported a binding-induced DNAzyme motor triggered by the survivin mRNA, which was a one-to-more signal-triggered model (one target triggered more signals), amplifying the detection signal and enhancing the sensitivity. The nanomotor is constructed by assembling several DNAzyme motor strands silenced by the blocker strands, and dozens of FAM-labeled substrate strands on a single gold nanoparticle (AuNP), forming three-dimensional DNA tracks. Through building the survivin mRNA bridge between the blocker and the DNAzyme motor strand, the binding-induced DNA nanomotor could be triggered by survivin mRNA. The operation of the DNAzyme motor was self-powered. And each walking step of the DNAzyme motor was fueled by DNAzyme-catalyzed substrate cleavage, along with the cleavage of the fluorescent molecule, resulting in autonomous and progressive walking along the AuNP-based tracks, and the fluorescence increase. The DNAzyme motor exhibited excellent sensitivity and remarkable specificity for survivin mRNA, providing the potential for cell image.

Refinement method for compressive hyperspectral data cubes based on self-fusion.

Compressive hyperspectral images often suffer from various noises and artifacts, which severely degrade the imaging quality and limit subsequent applications. In this paper, we present a refinement method for compressive hyperspectral data cubes based on self-fusion of the raw data cubes, which can effectively reduce various noises and improve the spatial and spectral details of the data cubes. To verify the universality, flexibility, and extensibility of the self-fusion refinement (SFR) method, a series of specific simulations and practical experiments were conducted, and SFR processing was performed through different fusion algorithms. The visual and quantitative assessments of the results demonstrate that, in terms of noise reduction and spatial-spectral detail restoration, the SFR method generally is much better than other typical denoising methods for hyperspectral data cubes. The results also indicate that the denoising effects of SFR greatly depend on the fusion algorithm used, and SFR implemented by joint bilateral filtering (JBF) performs better than SRF by guided filtering (GF) or a Markov random field (MRF). The proposed SFR method can significantly improve the quality of a compressive hyperspectral data cube in terms of noise reduction, artifact removal, and spatial and spectral detail improvement, which will further benefit subsequent hyperspectral applications.

Practical generation of arbitrary high-order cylindrical vector beams by cascading vortex half-wave plates.

A practical direct-view scheme for generating arbitrary high-order cylindrical vector (HCV) beams by cascading vortex half-wave plates (VHPs) is presented. The combination of odd number 2n-1 VHPs for n≥1 can realize (m2n-1-m2n-2+…+m1)-order CV beams, in which m is the order number of VHP and the corresponding subscript 2n-1 represents the arrangement number of VHPs, and the cascading of even number 2n ones can obtain (m2n-m2n-1+…+m2-m1)-order CV beams. All 1-12 order CV beams, including the high-order anti-vortex CV (ACV) beams, are generated only by selectively cascading the VHPs with m=1, 3 and 8. The polarization properties of the generated HCV beams are investigated by measuring the corresponding Stokes parameters. It is experimentally demonstrated that arbitrary HCV beams are effectively achieved by the proposed method. The order numbers of CV beams can be greatly expanded by cascading limited types of VHPs.

Analysis of the Influence of Shrinkage Tensile Stress in Potting Material on the Anti-Overload Performance of the Circuit Board.

In this article, the influence of shrinkage tensile stress in potting materials on the anti-overload performance of a circuit board was studied. Firstly, the phenomenon of shrinkage tensile stress in common potting materials was analyzed, and it was found that the commonly used potting adhesives displayed large shrinkage characteristics. Secondly, a small experiment was set up to verify that the shrinkage tensile stress of potting adhesives would lead to printed circuit board (PCB) deformation, and the shrinkage stress was contrary to the acceleration direction of overload. Thirdly, the influence of potting adhesives on the overload resistance of the PCB was analyzed. However, the shrinkage tensile stress in the potting adhesive weakened the anti-overload ability of the circuit board. When there was a small amount of expansion stress in the potting adhesive, the overload resistance of the circuit board could be partially increased. From the analysis, it is indicated that a material with a certain expansion property, elasticity, and dense structure should be selected as the potting adhesive. This article provides a reference for improving the overload resistance of electronic devices.

A dicyanoisophorone-based, near-infrared, lysosome-targeting pH sensor with an extremely large Stokes shift.

Intracellular pH plays an important role in various biological processes; abnormal pH changes in the intracellular compartment leads to the production of free radicals, the disruption of membrane contractility, inappropriate apoptosis, and necrosis, resulting in serious illness. Although fluorescent probes have widely been used to detect pH levels owing to their high sensitivity and specificity, there is still a demand for near-infrared (NIR) fluorescent probes with high Stokes shift. Here, a NIR fluorescent probe, PipDC, comprising N-ethyl piperazine (response unit) and naphthyl dicyanoisophorone (fluorophore), was designed for pH sensing. The probe has an extremely large Stokes shift (290 nm), and its fluorescence intensity at 730 nm sharply increases when the environment changes from basic to acidic owing to the protonation of piperazine, which results in the quenching of the photoinduced electron transfer effect. It exhibited a specific response to acidic microenvironments regardless of other interfering substances. In addition, PipDC operates well in the lysosome environment in living cells and displays an off-on fluorescence response with pH alterations. Together, these results suggest that PipDC is a promising fluorescent probe for intracellular pH sensing.

Introduction of an interface layer on hydroxyapatite whisker/poly(L-lactide) composite and its contribution for improved bioactivity and mechanical properties.

A hydroxyapatite whisker (w-HA) was synthesized via dissolution-precipitation by forming calcium-ethylene diamine tetra acetic acid (Ca-EDTA) complexing. The hydroxyapatite whisker was formed with precipitation of Ca2+ along the c-axis due to the space inhibition of Ca-EDTA complex during refluxing. The op-w-HA (oligomeric poly(lactic acid) modified w-HA), p-w-HA (poly(L-lactide) modified w-HA) and pc-w-HA (poly(L-lactide) and cyclodextrin modified w-HA) were obtained via the surface modification of w-HA. The particle size, surface charge and biocompatibility of theses modified w-HA particles were successfully adjusted. Among these materials, pc-w-HA exhibited nearly no toxicity, better adhesion to mesenchymal stem cells (MSCs) (5 times better than w-HA) and greater osteoinductivity among the obtained materials (40% of mineralized extracellular matrix higher than w-HA) due to better surface properties. Different kinds of powders (w-HA, p-w-HA and pc-w-HA) were blended with PLLA (poly(L-Lactide)) to form a composite material, respectively. The pc-w-HA/PLLA composite showed better mechanical properties (tensile strength of the pc-w-HA/PLLA composite was 22.3% higher than that of w-HA/PLLA), which could be attributed to mainly two factors including the structure preservation of w-HA bundles and pseudorotaxane linkage between PLA-cyclodextrin and PLLA. The MSCs adhesion of the pc-w-HA/PLLA composite was much better due to balanced hydrophilicity/hydrophobicity and surface roughness. This surface modification method could provide a new and effective strategy for the preparation of bioresorbable composite material with great bioactivity and mechanical property, which has great potential in the medical device industry.

Surgery of the Primary Tumor Offers Survival Benefits of Breast Cancer with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis.

BACKGROUND: Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. METHODS: This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. RESULTS: A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. CONCLUSION: For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

ARG1 functions as a tumor suppressor in breast cancer.

Arginase I (ARG1) is a cytosolic enzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The association of ARG1 with cancer has mostly been focused on the ARG1 released by tumor-associated myeloid cells in tumor microenvironment. However, the role of ARG1 expressed in cancer cells is unclear. Here, we showed that the expression of ARG1 in human breast cancer (BC) is related to a good prognosis in BC patients. Overexpression of ARG1 suppresses BC cell proliferation and migration in vitro and xenograft tumor growth and development in mouse models. Furthermore, ARG1 expression down-regulates the expression of p-AKT, leading to the de-activation of AKT signal pathway in BC cells. Thus, our results established that in contrast to the role of ARG1 released from tumor-associated myeloid cells in tumor microenvironment that promotes tumor immune escape, ARG1 expressed in BC cells suppresses AKT signaling pathway and functions as a tumor suppressor.

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer.

Breast cancer is the most common malignancy among women worldwide. Kynureninase (KYNU) located in 2q22.2, which was associated with tryptophan utilization and metabolic diseases including cardiac, renal and limb defects syndrome 2. However, the role of KYNU in breast cancer (BC) development remains unclear. The expression of KYNU was examined by immunohistochemistry (IHC) in 137 primary BC tissues, and the correlation of KYNU expression with clinical pathological characteristics and the biomarkers (ER, PR, HER2, E-cad and Ki-67) was analysed. The role of KYNU in cancer cell proliferation, tumour growth and development was evaluated by MTT assay, soft agar colony formation assay and xenograft mouse models. Among 137 primary BC tissues, 46.7% (64/137) had high KYNU expression (IHC scores >4) while 53.3% (73/137) had low KYNU expression (IHC scores ≤4). The expression of KYNU was positively correlated with the expressions of ER (P = .002), PR (P = .007) and E-cad (P = .03), while negatively associated with tumour grade (P = .008), tumour stage (P < .001) and the expressions of HER2 (P = .04) and Ki-67 (P = .019). Overexpression of KYNU significantly inhibited cell proliferation in cell culture, colony formation in soft agar and xenograft BC development in NOD/SCID mice. Kynureninase suppresses BC cell proliferation, tumour growth and development. Kynureninase may function as a tumour suppressor in BC.

Single-shot coherent power-spectrum imaging of objects hidden by opaque scattering media.

We report coherent imaging of objects behind opaque scattering media with only one piece of the power spectrum pattern. We solve the unique solution and improve algorithm speed for the inverse problem. Based on the proposed scattering-disturbance model, with only one piece of the Fourier transform power spectrum pattern under coherent illumination, we successfully reconstruct clear images of the objects fully hidden by an opaque diffuser. The experimental results demonstrate the feasibility of the reconstruction method and the scattering-disturbance model. Our method makes it possible to carry out snapshot coherent imaging of the objects obscured by scattering media, which extends the methodology of x-ray crystallography to visible-light scattering imaging for underwater and living biomedical imaging.

[Diagnostic value for the fine needle aspiration biopsy and contrast-enhanced ultrasound in thyroid imaging reported and data system Grade 4 nodules].

OBJECTIVE: To study the clinical application value of ultrasound-guided fine needle aspiration biopsy (US-FNAB) and contrast-enhanced ultrasound (CEU) in the diagnosis of thyroid imaging reported and data system Grade 4 (TI-RADS 4) nodules.
 Methods: A retrospective analysis of 134 patients with thyroid nodules surgery were selected, and their results of preoperative color Doppler ultrasonography were TI-RADS 4. The data of US-FNAB and CEU before operation and the results of pathological section after operation were collected. The pathological results were taken as the gold standard, and the specimens obtained by US-FNAB puncture were used for HE staining and cytological diagnosis. The sensitivity, specificity, accuracy and the cost were calculated for CEU and US-FNAB, respectively. The diagnostic efficacy of the 2 methods was compared.
 Results: Of 134 thyroid nodules, there were 131 malignant nodules (97.76%) and 3 benign ones (2.24%). The sensitivity of US-FNAB and CEU were 87.02% and 93.89% respectively. The specificity of US-FNAB and CEU were 100.00% and 66.67%. The accuracy of US-FNAB and CEU were 87.31% and 93.28% respectively. Comparisons of the diagnostic accuracy were performed by χ2 test. There was no significant difference in sensitivity between CEU and US-FNAB (P>0.05). However, the sensitivity of US-FNAB and CEU were 87.50% and 100.00%, respectively, when the maximum diameter of nodule was less than 10 mm, and there was statistical significance (P<0.05). The sensitivity of US-FNAB and CEU were 92.73% and 85.45%, respectively, when the maximum diameter of nodule was more than 10 mm, and there was no statistical significance (P>0.05). The cost and risk of US-FNAB was higher than those of CEU.
 Conclusion: The sensitivity of US-FNAB is higher than that of CEU for thyroid nodules with the diameter larger than 10 mm. With high detection rate, good safety and low cost, CEU can still be used for thyroid nodules with the diameter less than 10 mm, which is diagnosed as negative nodules by US-FNAB.

A TP73-AS1/miR-200a/ZEB1 regulating loop promotes breast cancer cell invasion and migration.

Breast cancer (BC) is one of the leading causes of cancer deaths worldwide and the most common cancer among women. In our previous study, we revealed that lncRNA TP73-AS1 promotes breast cancer cell proliferation through directly binding to miR-200a. Herein, we evaluated the effect of TP73-AS1 in breast cancer cell invasion and migration, and further demonstrated the direct binding between TP73-AS1 and miR-200a, between miR-200a and 3'UTR of ZEB1, an essential metastasis-related transcription factor. TP73-AS1 promoted ZEB1 expression via competing with ZEB1 3'UTR for miR-200a binding. Moreover, ZEB1 could bind to the promoter region of TP73-AS1 to activate its expression. TP73-AS1 and ZEB1 expression was up-regulated, whereas miR-200a expression was down-regulated in breast cancer tissues. Taken together, we demonstrated a TP73-AS1/miR-200a/ZEB1 regulating loop in breast cancer cells, which promote cancer cell invasion and migration through regulating E-cadherin and Twist expression. Suppressing TP73-AS1 expression to rescue miR-200a expression, thus to inhibit ZEB1 and Twist expression and up-regulate E-cadherin might improve breast cancer cell invasion and migration.

TP73-AS1 promotes breast cancer cell proliferation through miR-200a-mediated TFAM inhibition.

P73 antisense RNA 1T (TP73-AS1 or PDAM) is a long non-coding RNA, which can regulate apoptosis through regulation of p53 signaling-related anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in breast cancer (BC) growth and the underlying mechanism remain unclear so far. In the present study, the effect of TP73-AS1 in BC cell lines and clinical tumor samples was detected so as to reveal its role and function. In the present study, TP73-AS1 was specifically upregulated in BC tissues and BC cell lines and was correlated to a poorer prognosis in patients with BC. TP73-AS1 knocking down suppressed human BC cell proliferation in vitro through regulation of TFAM. In our previous study, we demonstrated that miR-200a inhibits BC cell proliferation through targeting TFAM; here we revealed that TP73-AS1 could regulate miR-200a through direct targeting. Moreover, TP73-AS1 might compete with TFAM for miR-200a binding thus to promote TFAM expression. Data from the present study revealed that TP73-AS1 promoted BC cell proliferation through acting as a competing endogenous RNA (ceRNA) by sponging miR-200a. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting BC cell proliferation and a potential target for human BC treatment.