Comparative efficacy of intraoperative radiotherapy and external boost irradiation in early-stage breast cancer: a systematic review and meta-analysis.

External boost radiotherapy (EBRT) and intraoperative radiotherapy (IORT) are shown to be effective in patients with early-stage breast cancer. However, the difference between IORT and EBRT for patients' prognosis remains to be elucidated. The purpose of this meta-analysis is to investigate differences in local recurrence (LR), distant metastases, disease free survival (DFS), and overall survival (OS) between these two therapies. We searched the Cochrane Library, PubMed, Web of Science and Embase, from inception to Jan 10th, 2022. We used The Cochrane risk-of-bias assessment tool to assess the risk of bias of the included studies, and the STATA15.0 tool was used for the meta-analyses. Eight studies were ultimately included. Meta-analysis demonstrated that there was an inconsistent finding in the long-term risk of LR between the two radiotherapies, and there was no significant difference in short-term risk of LR, the metastasis rate, DFS, and OS IORT would be more convenient, less time-consuming, less costly, and more effective at reducing side effects and toxicity. However, these benefits must be balanced against the potential for increased risk of LR in the long term.

Investigation of the Mechanism of hsa_circ_000 1429 Adsorbed miR-205 to Regulate KDM4A and Promote Breast Cancer Metastasis.

This study investigates the mechanism of hsa_circ_0001429 adsorbing miR-205 and regulating the expression of KDM4A to promote breast cancer metastasis and its mechanism. Mammary epithelial cells MCF-10A and human breast cancer cell lines BT474, SKBr-3, ZR-75-30, and MCF7 are cultured, and the mRNA expressions of hsa_circ_000 1429, miR-205, and KDM4A are detected by qRT-PCR; hsa_circ_000 1429 binds to miR-205, and miR-205 targets KDM4A. RIP verifies that hsa_circ_000 1429 binds to AGO2; RNA pull down results prove that hsa_circ_000 1429 binds to miR-205; MTT detects cell proliferation; transwell assay detects cell migration and invasion ability; flow cytometry detects cell apoptosis rate. The expressions of KDM4A, migration, and invasion-related factors, N-cadherin and MMP-9 protein, are detected by blot. hsa_circ_000 1429 may upregulate the KDM4A gene by adsorbing miR-205. Therefore, it will promote the proliferation, migration, and invasion of breast cancer cells and inhibit their apoptosis.

Upregulation of LINC00511 expression by DNA hypomethylation promotes the progression of breast cancer.

BACKGROUND: LINC00511 is a newly discovered long intergenic nonprotein-coding RNA (Ribonucleic acid) with unknown. METHOD: Differential gene expression analysis was performed on breast cancer microarray data, and the upregulated expression of LINC00511 in breast cancer tissues and breast cancer cell lines was verified by qRT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction). A cohort study revealed a correlation between the expression of LINC00511 and the clinicopathological features in breast cancer patients. The effects of LINC00511 on breast cancer migration and invasion were studied in vitro. Then, an experiment using the Illumina Infinium Human Methylation450 Beadchip data was conducted to study the role of DNA (Deoxyribonucleic acid) methylation in LINC00511 expression, and DAVID (Database for Annotation, Visualization and Integrated Discovery) Functional Annotation Bioinformatics Microarray Analysis was used to determine the biological functions and potential pathways of LINC00511 in breast cancer. Then, LINC00511 and key genes associated with breast cancer disease progression were further studied in TCGA (The Cancer Genome Atlas), and western blotting was used to verify the results at the protein level. Finally, we further studied the effect of LINC00511 on Panobinostat drug sensitivity in breast cancer and its effect on the prognosis of breast cancer patients. RESULTS: LINC00511 was upregulated in breast cancer patients. The expression of LINC00511 was closely related to lymph node metastasis, tumor size and molecular subtypes of breast cancer. The in vitro studies revealed that LINC00511 could promote the migration and invasion in MDA-MB-231 and MCF-7 cells. In terms of mechanism, DNA hypomethylation promoted the expression of LINC00511, furthermore LINC00511 promoted the expression of Wnt10A, E2F2, TGFA, and MET, which participate in the progression of breast cancer. In addition, LINC00511 reduced the sensitivity of breast cancer cells to Panobinostat. Moreover, breast cancer patients with a high expression of LINC00511 had a poor prognosis. CONCLUSIONS: DNA hypomethylation promotes the expression of LINC00511 in breast cancer, and LINC00511 promotes the progression of breast cancer by upregulating Wnt10A, E2F2, TGFA and MET. High expression of LINC00511 is associated with poor prognosis. Our study identified the mechanism of LINC00511 upregulation and provides novel information on the progression of breast cancer.

UBE2O promotes the proliferation, EMT and stemness properties of breast cancer cells through the UBE2O/AMPKα2/mTORC1-MYC positive feedback loop.

Ubiquitin-conjugating enzyme E2O (UBE2O) is a large E2 ubiquitin-conjugating enzyme that possesses both E2 and E3 ligase activities. Ectopic UBE2O overexpression is associated with a variety of human diseases, especially cancers. However, the expression profile and functional biology of UBE2O in human breast cancer (BC) remain unclear. In this study, we found that UBE2O was significantly overexpressed in human BC tissues and cells. Patients with high UBE2O expression tended to have a high risk of metastasis and poor prognosis. In vitro assays revealed that UBE2O promoted BC cell proliferation and epithelial-mesenchymal transformation (EMT) and endowed BC cells with cancer stemness properties (CSPs). UBE2O knockdown in MDA-MB-231 cells suppressed tumour growth and lung metastasis in MDA-MB-231 xenograft mouse models. Mechanistically, UBE2O functioned as a ubiquitin enzyme of AMPKα2, promoting its ubiquitination and degradation and thus activating the mTORC1 signal pathway and contributing to BC oncogenesis and metastasis. Furthermore, as a downstream factor of the UBE2O/AMPKα2/mTORC1 axis, the oncoprotein MYC transcriptionally promoted UBE2O and formed a positive feedback loop in human BC. Collectively, our study demonstrated that UBE2O/AMPKα2/mTORC1-MYC forms a positive feedback loop in human BC cells that regulates BC cell proliferation and EMT and endows BC cells with CSPs.