Color-Tunable Lead Halide Perovskite Single-Mode Chiral Microlasers with Exceptionally High glum.

Chiral microlasers hold great promise for optoelectronics from integrated photonic devices to high-density quantum information processing. Despite significant progress in lead-halide perovskite emitters, chiral lasing with high dissymmetry factors (glum) has not yet been realized. Here, we demonstrate chiral single-mode microlasers with exceptional stability and tunable emission across the visible range by combining CsPbClxBr3-x perovskite microrods (MRs) with a cholesteric liquid crystal (CLC) layer. The MRs lase via a whispering gallery mode (WGM) microcavity and confer chirality through the encapsulated CLC layer, thus exhibiting circularly polarized lasing with dissymmetry factors reaching 1.62. Importantly, we demonstrate wavelength-tunable high dissymmetry chiral lasers in a broad spectral range by tuning the halide composition and using CLC layers with the desired photonic bandgap (PBG). This facile approach to generate chiral lasing not only is applicable to semiconductor nano- and microcrystals but also paves the way for potential integration into nanoscale photonic devices.

circRAD18 sponges miR-208a/3164 to promote triple-negative breast cancer progression through regulating IGF1 and FGF2 expression.

As a new rising star of non-coding RNA, circular RNAs (circRNAs) emerged as vital regulators with biological functions in diverse of cancers. However, the function and precise mechanism of the vast majority of circRNAs in triple-negative breast cancer (TNBC) occurrence and progression have not been clearly elucidated. In the current study, we identified and further investigated hsa_circ_0002453 (circRAD18) by analyzing our previous microarray profiling. Expression of circRAD18 was found significantly upregulated in TNBC compared with normal mammary tissues and cell lines. circRAD18 was positively correlated with T stage, clinical stage and pathological grade and was an independent risk factor for TNBC patients. We performed proliferation, colony formation, cell migration, apoptosis and mouse xenograft assays to verify the functions of circRAD18. Knockdown of circRAD18 significantly suppressed cell proliferation and migration, promoted cell apoptosis and inhibited tumor growth in functional and xenograft experiments. Through luciferase reporter assays, we confirmed that circRAD18 acts as a sponge of miR-208a and miR-3164 and promotes TNBC progression through upregulating IGF1 and FGF2 expression. Altogether, our research revealed the pivotal role of circRAD18-miR-208a/3164-IGF1/FGF2 axis in TNBC tumorigenesis and metastasis though the mechanism of competing endogenous RNAs. Thus, circRAD18 may serve as a novel prognostic biomarker and potential target for TNBC treatment in the future.

miR-200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer.

Resistance to trastuzumab remains a major obstacle in HER2-overexpressing breast cancer treatment. miR-200c is important for many functions in cancer stem cells (CSCs), including tumour recurrence, metastasis and resistance. We hypothesized that miR-200c contributes to trastuzumab resistance and stemness maintenance in HER2-overexpressing breast cancer. In this study, we used HER2-positive SKBR3, HER2-negative MCF-7, and their CD44+ CD24- phenotype mammospheres SKBR3-S and MCF-7-S to verify. Our results demonstrated that miR-200c was weakly expressed in breast cancer cell lines and cell line stem cells. Overexpression of miR-200c resulted in a significant reduction in the number of tumour spheres formed and the population of CD44+ CD24- phenotype mammospheres in SKBR3-S. Combining miR-200c with trastuzumab can significantly reduce proliferation and increase apoptosis of SKBR3 and SKBR3-S. Overexpression of miR-200c also eliminated its downstream target genes. These genes were highly expressed and positively related in breast cancer patients. Overexpression of miR-200c also improved the malignant progression of SKBR3-S and SKBR3 in vivo. miR-200c plays an important role in the maintenance of the CSC-like phenotype and increases drug sensitivity to trastuzumab in HER2+ cells and stem cells.

circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer.

BACKGROUND: Increasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear. METHODS: We used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC. RESULTS: qRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375. CONCLUSIONS: The circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.

Characteristics of Friedel pairs and diffraction contrast tomography with non-perpendicular rotation axis.

The characteristics of Friedel pairs in diffraction contrast tomography (DCT) are studied in the condition that the rotation axis of the sample is not exactly perpendicular to the incident X-ray direction. For the rotation axis approximately aligned along the vertical direction, the Friedel pairs close to the horizontal plane are insensitive to the non-perpendicularity of the rotation axis, and can be used to refine the sample-to-detector distance and X-ray energy, while the Friedel pairs close to the vertical direction are sensitive to the non-perpendicularity of the rotation axis, and can be used to determine the rotation axis orientation. The correct matching proportion of Friedel pairs decreases with increasing non-perpendicularity of the rotation axis. A method of data processing considering rotation axis misalignment is proposed, which significantly increases the correct matching and indexing proportions of the diffraction spots. A pure aluminium polycrystalline sample is investigated using DCT at beamline 4W1A of Beijing Synchrotron Radiation Facility. Based on the analysis of Friedel pairs, the sample-to-detector distance and X-ray energy are refined to be 8.67 mm and 20.04 keV, respectively. The non-perpendicular angle of the rotation axis is calculated to be 0.10°. With these refined geometric parameters, the matching proportion of the spatial position of diffraction spots is 90.62%. Three-dimensional reconstruction of the sample with 13 grains is realised using the algebraic reconstruction technique. It is demonstrated that the precise correction of the orientation of the sample rotation axis is effective in DCT suffering from rotation axis misalignment, and the higher accuracy in determining the rotation axis is expected to improve the reconstruction precision of grains.

The biogenesis, function and clinical significance of circular RNAs in breast cancer.

Circular RNAs (circRNAs) are noncoding RNAs that form covalently closed loop structures. CircRNAs are dysregulated in cancer and play key roles in tumorigenesis, diagnosis, and tumor therapy. CircRNAs function as competing endogenous RNAs or microRNA sponges that regulate transcription and splicing, binding to proteins, and translation. CircRNAs may serve as novel biomarkers for cancer diagnosis, and they show potential as therapeutic targets in cancers including breast cancer (BC). In women, BC is the most common malignant tumor worldwide and the second leading cause of cancer death. Although evidence indicates that circRNAs play a critical role in BC, the mechanisms regulating the function of circRNAs in BC remain poorly understood. Here, we provide literature review aiming to clarify the role of circRNAs in BC and summarize the latest research. We provide a systematic overview of the biogenesis and biological functions of circRNAs, elaborate on the functional roles of circRNAs in BC, and highlight the value of circRNAs as diagnostic and therapeutic targets in BC.

LGR6 Promotes Tumor Proliferation and Metastasis through Wnt/ß-Catenin Signaling in Triple-Negative Breast Cancer.

Leucine-rich-repeat-containing G protein-coupled receptor 6 (LGR6) has been identified as the stem cell marker in multiple normal tissues and malignancies. Previous studies implicated paradoxical functions of LGR6 as a tumor-suppressor gene or oncogene given to the specific context. To explore the exact role of LGR6 in triple-negative breast cancer (TNBC) that never has been studied before, in this study, we assessed LGR6 expression levels by RT-PCR and immunohistochemistry. LGR6 stable expressing/silenced cells were established, and functional assays on tumor proliferation, as well as metastasis, were conducted both in vitro and in vivo. Here, we found that LGR6 was overexpressed in TNBC, which correlated with poor disease-free and overall survivals. Functional assays both in vitro and in vivo showed that LGR6 promotes tumor proliferation and metastasis. LGR6 also increased the ability of tumor spheroid formation. Underlying mechanism exploration further revealed that the oncogenic role of LGR6 might be associated with the Wnt/ß-catenin pathway. In conclusion, our findings first proved that LGR6 acts as an oncogene in (TNBC), indicating that LGR6 might be a potential therapeutic target for TNBC treatment.

Expression of glucose-regulated protein 78 as prognostic biomarkers for triple-negative breast cancer.

INTRODUCTION: Glucose-regulated protein78(GRP78) is a stress - induced endoplasmic reticulum chaperone protein. it is closely related to the occurrence, development, proliferation, differentiation and drug resistance of breast cancer. However, the association and clinicopathological features between GRP78 and triple negative breast cancer (TNBC) remain to be studied. MATERIAL AND METHODS: Clinical and pathological characteristics and overall survival were analysed retrospectively in 179 surgically resected TNBC patients. GRP78 was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs), and the association between GRP78 levels and clinicopathological factors and prognosis was analyzed. Furthermore, GRP78 expression in human TNBC and NTNBC cell lines was detected by Western blot and qRT-PCR. After Si-GRP78 knocked-down GRP78 in MDA-MB-231 and BT549 cell lines, cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and cell colony formation was detected by crystal violet staining, respectively. RESULTS: GRP78 was expressed in triple negative breast cancer (TNBC). GRP78 expression was significantly associated with invasive, distant metastasis and proliferation of TNBC (P<0.05). In addition, patients with positive GRP78 expression had shorter overall survival (OS) and disease-free survival (DFS). And the high expression of GRP78 was significantly associated with disease-free survival (DFS) in patients with TNBC (P<0.001). CONCLUSIONS: These findings improve our understanding of the expression pattern of GRP78 in TNBC and clarify the role of GRP78 as promising prognostic biomarkers for triple-negative breast cancer.

PARPBP is a prognostic marker and confers anthracycline resistance to breast cancer.

BACKGROUND: PARPBP (PARP1 binding protein) is an important suppressor of homologous recombination during DNA repair, but the expression and function of PARPBP in breast cancer remain unclear. METHODS: PARPBP expression was analyzed in breast cancer patient samples and public datasets for its correlation with clinical outcome. The function of PARPBP in breast cancer cell proliferation and anthracycline treatment response were studied both in vitro and in vivo. RESULTS: PARPBP was upregulated significantly at both mRNA and protein levels in breast cancer tissues compared with normal breast tissues. PARPBP high expression group had poorer overall survival (OS) than the PARPBP low expression group. Knockdown of PARPBP suppressed breast cancer cell proliferation and colony formation while overexpression of PARPBP did the opposite. We found that transcription factor forkhead box M1 (FOXM1) could activate PARPBP expression by directly binding to the promoter of PARPBP. In addition, high expression of PARPBP related with anthracycline resistance in breast cancer. Depletion of PARPBP increased breast cancer cell apoptosis and DNA damage caused by epirubicin. Moreover, tumor xenograft experiments further demonstrated that PARPBP was involved in breast cancer anthracycline resistance. CONCLUSION: Taken together, our results highlight that PARPBP is a prognostic marker and confers anthracycline resistance on breast cancer.

Correction to: Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer.

The original article [1] contains an error in Fig. 5b whereby two panels have been mistakenly duplicated. The correct version of Fig. 5b can be viewed ahead alongside the rest of Fig. 5.

Long non-coding RNA HUMT hypomethylation promotes lymphangiogenesis and metastasis via activating FOXK1 transcription in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with highly invasive ability and metastatic nature to the lymph nodes. Long non-coding RNAs (lncRNAs) have been widely explored in cancer tumorigenesis and progression. However, their roles in TNBC lymph node metastasis remains rarely studied. METHODS: The expression of lncRNA highly upregulated in metastatic TNBC (HUMT) in cell lines and tissues was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). RNA immunoprecipitation (RIP) and RNA pulldown were used to verify the interaction between lncRNA and protein. Chromatin immunoprecipitation (CHIP) and dCas9-gRNA-guided chromatin immunoprecipitation (dCas9-CHIP) were conducted to identify the specific binding site of HUMT-YBX1 complex. Western blot was used to detect the downstream of HUMT. RESULTS: HUMT was significantly upregulated in lymph node invasive cells and predicted poorer clinical prognosis. Functional study indicated that HUMT promoted lymphangiogenesis and lymph node metastasis. Bioinformatic analysis and qRT-PCR showed that the high expression of HUMT was correlated with the hypomethylation status of its promoter region. Further, HUMT recruited Y-box binding protein 1 (YBX1) to form a novel transcription complex and activated the expression of forkhead box k1 (FOXK1), thus enhancing the expression of vascular endothelial growth factor C (VEGFC). The therapeutic value was further validated in patient-derived xenograft (PDX) models, and a combined marker panel exhibited a better prognostic value for TNBC in receiver operating characteristic (ROC) analysis. CONCLUSIONS: Our study identified a novel TNBC lymph node metastasis-associated lncRNA, which promoted TNBC progression and indicated a novel biomarker and potential therapeutic target for TNBC lymph node metastasis.

MALAT1 and BACH1 are prognostic biomarkers for triple-negative breast cancer.

AIMS: The purpose of this study was to investigate the potential correlation between metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the transcription factor BTB and CNC homology 1 (BACH1) and their clinicopathological significance in triple-negative breast cancer (TNBC). SUBJECTS AND METHODS: MALAT1 and BACH1 were detected by immunohistochemistry using TNBC tissue microarrays of 240 patients. The association between MALAT1 and BACH1 expression levels was statistically analyzed. Moreover, the prognostic roles as well as clinical and pathological significance of MALAT1 and BACH1 expression in TNBC were determined. STATISTICAL ANALYSIS USED: Two-tailed Pearson correlation was used to examine the correlation of BACH1 and MALA1 expression. Comparisons of clinicopathological variables between different BACH1 and MALA1 expression groups were performed using χ2 tests. Overall survival (OS) and disease-free survival (DFS) curves were plotted with the Kaplan-Meier method and the differences in OS and DFS between three groups were compared by the log-rank test. Multiple comparisons were performed using χ2 tests for subsequent individual group comparisons. RESULTS: MALAT1 and BACH1 expression was significantly correlated with tumor-node-metastasis stage, distant metastasis, pathological stage, and survival outcomes of patients. Patients with high MALAT1 and BACH1 expression exhibited shorter overall survival and disease-free survival. CONCLUSIONS: These findings provide further insight into the expression pattern of MALAT1 and BACH1 in TNBC and suggest them as prognostic biomarkers for TNBC.

CircPLK1 sponges miR-296-5p to facilitate triple-negative breast cancer progression.

Aim: To investigate the role of circRNAs in triple-negative breast cancer (TNBC) and the underlying mechanisms. Materials & methods: We performed circRNA microarrays to explore the expression profiles of TNBC cell lines. Experiments in vitro and in vivo were conducted to explore the effects of circPLK1 on tumor proliferation and metastasis as well as the interaction between circPLK1, miR-296-5p and PLK1 in TNBC. Results & conclusion: CircPLK1 was significantly upregulated in TNBC and associated with poor survivals. CircPLK1 knockdown inhibited cell growth and invasion in vitro as well as tumor occurrence and metastasis in vivo. CircPLK1-miR-296-5p-PLK1 axis regulates tumor progression by ceRNA mechanism in TNBC, indicating that circPLK1 may serve as a prognostic factor and novel therapeutic target for TNBC.

circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185-aa Protein in Triple-Negative Breast Cancer.

Accumulating evidence indicates that circular RNAs (circRNAs) are vital regulators of various biological functions involved in the progression of multiple cancers. Circular F-box and WD repeat domain containing 7 (circFBXW7) (hsa_circ_0001451) has been reported to act as a tumor suppressor by encoding a novel protein in glioma; however, its functions and mechanisms in triple-negative breast cancer (TNBC) remain elusive. In the current study, we validated by qRT-PCR that circFBXW7 was downregulated in TNBC cell lines and found that low expression of circFBXW7 was associated with poorer clinical outcomes. circFBXW7 expression was negatively correlated with tumor size and lymph node metastasis, and it was an independent prognostic factor for TNBC patients. We performed cell proliferation, colony formation, transwell, wound-healing, and mouse xenograft assays to confirm the functions of circFBXW7. Overexpression of circFBXW7 obviously inhibited cell proliferation, migration, and tumor growth in both in vitro and in vivo assays. Luciferase reporter assays and RNA immunoprecipitation assays revealed that circFBXW7 serves as a sponge of miR-197-3p and suppresses TNBC growth and metastasis by upregulating FBXW7 expression. In addition, the FBXW7-185aa protein encoded by circFBXW7 inhibited the proliferation and migration abilities of TNBC cells by increasing the abundance of FBXW7 and inducing c-Myc degradation. In summary, our research demonstrated that circFBXW7 sponges miR-197-3p and encodes the FBXW7-185aa protein to suppress TNBC progression through upregulating FBXW7 expression. Thus, circFBXW7 may act as a therapeutic target and prognostic biomarker for TNBC.