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BackgroundAccumulating evidence suggests that circular RNAs (circRNAs) play critical roles in carcinomas. However, the contributions of circRNAs to breast cancer remain unclear. Herein, we determined the role of circZNF609 in breast cancer.MethodsA total of 143 breast cancer and 38 normal tissues were collected to assess the expression of circZNF609 and its relationship with breast cancer prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circZNF609 in breast cancer progression and its underlying molecular mechanisms.ResultsCircZNF609 was markedly over-expressed in breast cancer tissues and cell lines, and high circZNF609 expression was closely associated with poor outcome. Silencing of circZNF609 inhibited the malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circ-ZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover, miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of circZNF609 in breast cancer. In addition, clinically, a strong negative correlation was observed between the expression of circZNF609 and miR-145-5p in breast cancer tissues (r=–0.597, P<0.001), whereas a positive correlation between circZNF609 and p70S6K1 expression (r=0.319, P<0.001).ConclusionThese data suggest that circZNF609 contributes to breast cancer progression, at least partly, by modulating the miR-145-5p/p70S6K1 axis, and it may be a potential therapeutic target for breast cancer.

HER2‐positive breast cancer is an aggressive subtype of breast cancer, characterized by high malignancy and poor prognosis. Trastuzumab, the first HER2‐targeted monoclonal antibody therapy, has a crucial role in a curative setting in HER2‐positive breast cancer. However, frequent drug resistance inhibits its clinical efficacy. Herein, by performing circular RNA (circRNA) profiling, we identified a novel circRNA, circ‐BGN, as a key contributor in trastuzumab resistance. Circ‐BGN was evidently increased in trastuzumab‐resistant breast cancer cells and tissues, linking to poor overall survival. Knockdown of circ‐BGN inhibited breast cancer cell viability and notably restored its sensitivity to trastuzumab. Further, we found that circ‐BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1‐mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis, a newly recognized form of cell death that is distinct from apoptosis, necrosis, and autophagy. Moreover, erastin, a small‐molecule ferroptosis inducer, could effectively restore the anti‐tumor effect of trastuzumab. Pre‐clinically, the orthotopic tumor model showed that erastin significantly reduced tumor volume generated by trastuzumab‐resistant breast cancer cells, which was more pronounced after combined circ‐BGN knockdown. Collectively, our data reveal a novel circRNA controlling trastuzumab resistance via regulation of ferroptosis, providing a promising therapeutic strategy for trastuzumab‐resistant breast cancer patients.

The ground ice content in permafrost serves as one of the dominant properties of permafrost for the study of global climate change, ecology, hydrology and engineering construction in cold regions. This paper initially attempts to assess the ground ice volume in permafrost layers on the Qinghai-Tibet Plateau by considering landform types, the corresponding lithological composition, and the measured water content in various regions. An approximation demonstrating the existence of many similarities in lithological composition and water content within a unified landform was established during the calculations. Considerable knowledge of the case study area, here called the Source Area of the Yellow (Huanghe) River (SAYR) in the northeastern Qinghai-Tibet Plateau, has been accumulated related to permafrost and fresh water resources during the past 40 years. Considering the permafrost distribution, extent, spatial distribution of landform types, the ground ice volume at the depths of 3.0-10.0 m below the ground surface was estimated based on the data of 101 boreholes from field observations and geological surveys in different types of landforms in the permafrost region of the SAYR. The total ground ice volume in permafrost layers at the depths of 3.0-10.0 m was approximately (51.68 ± 18.81) km 3 , and the ground ice volume per unit volume was (0.31 ± 0.11) m 3 /m 3. In the horizontal direction, the ground ice content was higher in the landforms of lacustrine-marshland plains and alluvial-lacustrine plains, and the lower ground ice content was distributed in the erosional platforms and alluvial-proluvial plains. In the vertical direction, the volume of ground ice was relatively high in the top layers (especially near the permafrost table) and at the depths of 7.0-8.0 m. This calculation method will be used in the other areas when the necessary information is available, including landform type, borehole data, and measured water content.

Breast cancer is the most common malignancy among women and the leading cause of cancer deaths, with complicated pathogenesis that is largely unknown. In this study, we identified a novel long non-coding RNA (lncRNA) as a critical driver of breast cancer tumorigenesis. RUNX1 intronic transcript 1 (RUNX1-IT1) was notably overexpressed in human breast cancer tissues, and knockdown of RUNX1-IT1 inhibited breast cancer cell viability and invasion, as well as tumor growth in orthotopic transplantation model. Further, RUNX1-IT1 repressed ferroptosis, a novel iron-dependent form of regulated cell death, via increasing glutathione peroxidase 4 (GPX4) expression. Specifically, RUNX1-IT1 directly bound to N6-methyladenosine m6A reader IGF2BP1 and promoted the formation of (insulin like growth factor 2 mRNA binding protein 1) IGF2BP1 liquid-liquid phase separation (LLPS) biomolecular condensates, resulting in more IGF2BP1 occupation on GPX4 mRNA, increasing GPX4 mRNA stability. Moreover, high RUNX1-IT1 was linked to poor prognosis, and a strong positive correlation between RUNX1-IT1 and GPX4 was observed in clinical breast cancer tissues. Taken together, our data reveal that RUNX1-IT1 promotes breast cancer carcinogenesis through blocking ferroptosis via elevating GPX4, targeting of the previously unappreciated regulatory axis of RUNX1-IT1/IGF2BP1/GPX4 may be a promising treatment for patient with breast cancer.

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Myc is a well-known proto-oncogene that is frequently amplified and activated in breast cancer, especially in triple-negative breast cancer (TNBC). However, the role of circular RNA (circRNA) generated by Myc remains unclear. Herein, we found that circMyc (hsa_circ_0085533) was remarkably upregulated in TNBC tissues and cell lines, which was attributed to gene amplification. Genetic knockdown of circMyc mediated by lentiviral vector significantly inhibited TNBC cell proliferation and invasion. Importantly, circMyc increased cellular triglycerides, cholesterols and lipid droplet contents. CircMyc was detected in both cytoplasm and nucleus, cytoplasmic circMyc could directly bind to HuR protein, facilitating the binding of HuR to SREBP1 mRNA, resulting in increasing SREBP1 mRNA stability. Nuclear circMyc bound to Myc protein, facilitating the occupation of Myc on SREBP1 promoter, leading to increasing SREBP1 transcription. As a result, the elevated SREBP1 increased the expression of its downstream lipogenic enzymes, enhancing lipogenesis and TNBC progression. Moreover, the orthotopic xenograft model showed that depletion of circMyc markedly inhibited lipogenesis and reduced tumor size. Clinically, high circMyc was closely related to larger tumor volume, later clinical stage and lymph node metastasis, functioning as an adverse prognostic factor. Collectively, our findings characterize a novel Myc-derived circRNA controlling TNBC tumorigenesis via regulation of metabolic reprogramming, implying a promising therapeutic target.

In permafrost regions, buried oil pipelines have a substantial thermal impact on the surrounding permafrost due to the large temperature difference between the oil and ground. The change in the thermal regime of the permafrost may trigger frost heave and thaw settlement of the pipeline, and can even destroy the pipeline. In this paper, an example of parallel-buried pipelines is performed, and a numerical method is employed to simulate the thermal impact of pipelines on permafrost foundations for both ice-poor and ice-rich permafrost with various kinds of distances between parallel pipelines. The results show that the thermal effect caused by the operation of pipelines can increase the temperature of permafrost, as well as cause the underlying permafrost foundation to thaw gradually. The thermal impact of parallel pipelines on the permafrost foundation depends on the distance between the parallel pipelines, ice content of the permafrost, initial permafrost temperature, and so on. The degree of influence on each other decreases as the distance between parallel pipelines increases. With an insulated pipeline that has been in operation for 50 years, the thaw depths under the parallel pipelines, with distances of 5 m, 10 m, and 15 m, increase by 1.4 m, 0.4 m, and 0.1 m compared to the single pipeline in the ice-rich permafrost district with the average ground temperature being -0.5°C and the ice content being 35%. Nevertheless, there is no difference between the single and parallel pipelines if the distance is more than 20 m. The recommended distance between parallel pipelines in this district should be greater than 15 m. Different permafrost districts should set separate recommended distances, and the corresponding protective measures should be made outside the recommended distance.