Search

Circular RNAs (circRNAs) have been shown to modulate gene expression and participate in the development of multiple malignancies. The purpose of this study was to investigate the role of circ_0008039 in breast cancer (BC). The expression of circ_0008039, miR‐140‐3p, and spindle and kinetochore‐associated protein 2 (SKA2) was detected by qRT‐PCR. Cell viability, colony formation, migration, and invasion were evaluated using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay, colony formation assay, and transwell assay, respectively. Glucose consumption and lactate production were measured using commercial kits. Protein levels of hexokinase II (HK2) and SKA2 were determined by western blot. The interaction between miR‐140‐3p and circ_0008039 or SKA2 was verified by dual‐luciferase reporter assay. Finally, a mouse xenograft model was established to investigate the roles of circ_0008039 in BC in vivo. We found that circ_0008039 and SKA2 were upregulated in BC tissues and cells, while miR‐140‐3p was downregulated. Knockdown of circ_0008039 suppressed BC cell proliferation, migration, invasion, and glycolysis. Moreover, miR‐140‐3p could bind to circ_0008039 and its inhibition reversed the inhibitory effect of circ_0008039 interference on proliferation, migration, invasion, and glycolysis in BC cells. SKA2 was verified as a direct target of miR‐140‐3p and its overexpression partially inhibited the suppressive effect of miR‐140‐3p restoration in BC cells. Additionally, circ_0008039 positively regulated SKA2 expression by sponging miR‐140‐3p. Consistently, silencing circ_0008039 restrained tumor growth via increasing miR‐140‐3p and decreasing SKA2. In conclusion, circ_0008039 downregulation suppressed BC cell proliferation, migration, invasion, and glycolysis partially through regulating the miR‐140‐3p/SKA2 axis, providing an important theoretical basis for treatment of BC. [ABSTRACT FROM AUTHOR]

Background: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. Methods: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance. Results: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level. Conclusion: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment. [ABSTRACT FROM AUTHOR]

Trastuzumab has been widely used for treatment of HER-2-positive breast cancer patients, however, the clinical response has been restricted due to emergence of resistance. Recent studies indicate that long noncoding RNA AGAP2-AS1 (lncRNA AGAP2-AS1) plays an important role in cancer resistance. However, the precise regulatory function and therapeutic potential of AGAP2-AS1 in trastuzumab resistance is still not defined. In this study, we sought to reveal the essential role of AGAP2-AS1 in trastuzumab resistance. Our results suggest that AGAP2-AS1 disseminates trastuzumab resistance via packaging into exosomes. Exosomal AGAP2-AS1 induces trastuzumab resistance via modulating ATG10 expression and autophagy activity. Mechanically, AGAP2-AS1 is associated with ELAVL1 protein, and the AGAP2-AS1-ELAVL1 complex could directly bind to the promoter region of ATG10, inducing H3K27ac and H3K4me3 enrichment, which finally activates ATG10 transcription. AGAP2-AS1-targeting antisense oligonucleotides (ASO) substantially increased trastuzumab-induced cytotoxicity. Clinically, increased expression of serum exosomal AGAP2-AS1 was associate with poor response to trastuzumab treatment. In conclusion, exosomal AGAP2-AS1 increased trastuzumab resistance via promoting ATG10 expression and inducing autophagy. Therefore, AGAP2-AS1 may serve as predictive biomarker and therapeutic target for HER-2+ breast cancer patients., Competing Interests: None., (AJCR Copyright © 2021.)

Background: Most secondary transmission of COVID-19 is occurring in a hospital setting. To decrease person-to-person contact, health care providers have built many isolation wards. However, out-of-hospital professionals cannot access patient information, which has greatly reduced the efficiency of treatment; it is inconvenient for health care professionals to issue a case discussion with professionals from other wards. This article mainly introduces a mobile telehealth system (MTS) applied to facilitate patient information presentation and case discussion. Materials and Methods: The MTS searches patient information, which is stored in hospital intranet, and uses five modules to display patient information. By a request/response module and a real-time interaction module, we successfully conducted case discussions. In addition, we took measures in three areas to prevent patient information leakage. Results: The system uses mobile collaboration technology to present patient information and support case discussion. MTS was officially launched for 37 days, during which it has been used 3,061 times. Conclusions: The building of the MTS not only provides convenience and benefit for health care professionals, but also reduces person-to-person contact.

Long non-coding RNA gastric carcinoma high-expressed transcript 1 (lncRNA GHET1) is highly expressed in many tumors. The aim of the present study was to determine whether GHET1 inhibition decreases growth and metastasis of MCF-7 breast cancer cells by modulating epidermal growth factor receptor (EGFR) expression. In vitro, lncRNA GHET1 knockdown suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis by maintaining MCF-7 cells in the G1 phase of the cell cycle. Furthermore, lncRNA GHET1 knockdown reduced the expression of EGFR and related proteins. Treatment of mice with a GHET1 inhibitor prevented tumor growth in vivo. The results indicate that lncRNA GHET1 inhibition directly suppresses EGFR expression, significantly inhibiting the downstream PI3K/AKT/Cyclin D1/MMP2/9 pathway. This mechanism may underlie the suppression of breast cancer cell activities including proliferation, migration, and invasion. In conclusion, lncRNA GHET1 knockdown suppresses tumor growth and metastasis by suppressing the activity of EGFR and downstream pathways., Competing Interests: None.