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The quality control testing component and main active ingredient of Polygonum multiflorum Thunb. (P. multiflorum), known as trans-2,3,5,4ʹ-tetrahydroxystilbene 2-O-β-D-glucopyranoside (TSG), exhibits diverse biological activities. In this study, we report, for the first time, the potent ability of TSG to induce ferroptosis in triple negative breast cancer (TNBC) cell lines and to inhibit the proliferation of TNBC cells. Treatment with TSG triggers the production of lipid peroxides, 4-hydroxynonenal (4-HNE), and reactive oxygen species (ROS) in TNBC cells, indicating the induction of ferroptosis. Both in vivo and in vitro experiments confirmed the inhibitory effects of TSG on TNBC cell proliferation and metastasis. Furthermore, we investigated the effects of other stilbene glycoside oligomers, alongside TSG, on TNBC cell lines. These compounds also demonstrated the ability to induce ferroptosis and suppress TNBC cells’ proliferation and metastasis. These findings suggest that the induction of ferroptosis by TSG and related compounds could potentially serve as a promising therapeutic strategy for TNBC treatment. Graphical Abstract

BackgroundEnhanced de novo lipogenesis is essential for hepatocellular carcinoma (HCC). Abnormally high cullin-associated and neddylation-dissociated 1 (CAND1) expression is associated with poor clinical prognosis in HCC. The SKP1-Cullin-1-F-box (SCF) complex consists of the SKP1, Cullin-1 and F-box proteins (FBPs) and performs multiple functions including adipogenesis. SCF complex was modulated by CAND1, but Whether and how the CAND1 promotes HCC by regulating SCF complex and lipogenesis are unknown.MethodsHCC samples were used to analyze the correlations between CAND1 expression and clinicopathological characteristics such as survival and prognosis. The in vitro functions of CAND1, FBXO11 and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) were measured by cell proliferation, colony formation and migration assays. The in vivo functions were tested in multiple mouse liver cancer models including patient-derived xenograft (PDX), cell line-derived xenograft and AKT/NRASV12-induced primary liver cancer models. Injections of adeno-associated virus targeting CAND1 (AAV-shCAND1) were performed to evaluate the therapeutic efficacy of targeting CAND1. RNA-Seq and lipidomic assays followed by serial biochemical experiments including mass spectrometry, immunoprecipitation and GST pull-down were performed to dissect the underlying mechanisms.ResultsCAND1 promoted the expression of lipid synthesis genes by disrupting SCF complex assembly and lipid accumulation. Furthermore, we identified hnRNPA2B1 as a novel F-box protein 11 (FBXO11)-binding partner. FBXO11 directly bound to hnRNPA2B1 and promoted hnRNPA2B1 ubiquitination and subsequent degradation. Our evaluations of the therapeutic efficacy of AAV-shCAND1 injections confirmed that targeting the CAND1-SCFFBXO11-hnRNPA2B1A signalling axis was therapeutically effective. CAND1 downregulation significantly reduced the tumour burden in a primary mouse liver cancer model and a PDX model.ConclusionsOur results highlight that CAND1 is associated with poor prognosis in HCC and regulates lipid metabolic reprogramming by dissociating the SCF complex. Targeting the CAND1-SCFFBXO11-hnRNPA2B1 axis may be a novel strategy for HCC treatment.

TGF‐β1 is the strongest cytokine known to promote liver fibrosis. It has been previously demonstrated that the activation of TGF‐β1 initiates a temporary collagen accumulation program, which is important for wound repair in several organs. Furthermore, temporary extracellular matrix enhancement often leads to progressive fibrosis, which is accountable for cases of severe morbidity and mortality worldwide. However, its action mechanism has not been fully explored. It was previously reported that UCA1 could promote its occurrence and development in various tumors. Importantly, it was reported that TGF‐β1 could activate the expression of UCA1 in liver cancer, gastric cancer, and breast cancer. However, the role of UCA1 in organ fibrosis, including liver fibrosis, remains unreported. The present study reported for the first time that TGF‐β1/Smad3 could promote liver fibrosis by upregulating UCA1, which further affected DKK1 and collagen, such as COL1A1, COL1A2, and COL3A1. Meanwhile, UCA1 could competitively bind with miR18a to stabilize Smad3 to constitute a positive feedback pathway, which played a significant role in the promotion of liver fibrosis. Altogether, the present study provides a theoretical basis for devising promising treatment strategies for liver fibrosis.Key messagesUCA1 was found to promote the progression of liver fibrosis in vitro.UCA1 is regulated by TGF-β1 and promotes liver fibrosis through the canonical Smad pathway.UCA1 can competitively bind with miR18a, promote liver fibrosis by stabilizing Smad3, and form a UCA1-miR18a/Smad3 positive feedback.UCA1 binds EZH2 to inhibit the DKK1 expression and promote liver fibrosis.

Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the identification of novel therapeutic targets for treating cancer. Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family that is involved in the progression of various cancers, including medulloblastoma, primitive neuroectodermal brain tumors, and breast cancer. NTF3 is under-expressed in human hepatocellular carcinoma (HCC), albeit its specific effects and the action mechanism have not been elucidated. Here, we confirmed that NTF3 expression was significantly low in HCC with reference to the GSEA database. By collecting patient data from our center and performing qRT-PCR analysis, we found that expression was significantly downregulated in 74 patients with HCC. Low NTF3 expression was associated with a shorter overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Both and experiments revealed that NTF3 considerably inhibited the progression of HCC cells. We found that the ligand NTF3 is regulated by c-Jun and binds to the p75 neurotrophin receptor (p75NTR) and then activates the JNK and P38 MAPK pathways to induce apoptosis. Entinostat (the target of HDAC1/HDAC3) can activate the NTF3/p75NTR pathway. These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC.

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer deaths globally. Although considerable progress has been made in the treatment, clinical outcomes of HCC patients are still poor. Therefore, it is necessary to find novel prognostic factors upon which prevention and treatment strategies can be formulated. Ficolin-3 (FCN3) protein is a member of the human ficolin family. It activates complement through pathways associated with mannose-binding lectin-associated serine proteases. Herein, we identified that FCN3 was downregulated in HCC tissues and decreased FCN3 expression was closely related to poor prognosis. Overexpression of FCN3 induced apoptosis and inhibited cell proliferation via the p53 signaling pathway. Mechanistically, FCN3 modulated the nuclear translocation of eukaryotic initiation factor 6 (EIF6) by binding ribosome maturation factor (SBDS), which induced ribosomal stress and activation of the p53 pathway. In addition, Y-Box Binding Protein 1 (YBX1) involved in the transcription and translation level regulation of FCN3 to SBDS. Besides, a negative feedback loop in the downstream of FCN3 involving p53, YBX1 and SBDS was identified.

Centromere protein U (CENPU), a centromere-binding protein required for cellular mitosis, has been reported to be closely associated with carcinogenesis in multiple malignancies; however, the role of CENPU in hepatocellular carcinoma (HCC) is still unclear. Herein, we investigated its biological role and molecular mechanism in the development of HCC. High CENPU expression in HCC tissue was observed and correlated positively with a poor prognosis in HCC patients. CENPU knockdown inhibited the proliferation, metastasis, and G1/S transition of HCC cells and , while ectopic expression of CENPU exerted the opposite effects. Mechanistically, CENPU physically interacted with E2F6 and promoted its ubiquitin-mediated degradation, thus affecting the transcription level of E2F1 and further accelerating the G1/S transition to promote HCC cell proliferation. E2F1 directly binds to the CENPU promoter and increases the transcription of CENPU, thereby forming a positive regulatory loop. Collectively, our findings indicate a crucial role for CENPU in E2F1-mediated signalling for cell cycle progression and reveal a role for CENPU as a predictive biomarker and therapeutic target for HCC patients.

Enhanced de novo lipogenesis is essential for hepatocellular carcinoma (HCC). Abnormally high cullin-associated and neddylation-dissociated 1 (CAND1) expression is associated with poor clinical prognosis in HCC. The SKP1-Cullin-1-F-box (SCF) complex consists of the SKP1, Cullin-1 and F-box proteins (FBPs) and performs multiple functions including adipogenesis. SCF complex was modulated by CAND1, but Whether and how the CAND1 promotes HCC by regulating SCF complex and lipogenesis are unknown. HCC samples were used to analyze the correlations between CAND1 expression and clinicopathological characteristics such as survival and prognosis. The in vitro functions of CAND1, FBXO11 and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) were measured by cell proliferation, colony formation and migration assays. The in vivo functions were tested in multiple mouse liver cancer models including patient-derived xenograft (PDX), cell line-derived xenograft and AKT/NRASV12-induced primary liver cancer models. Injections of adeno-associated virus targeting CAND1 (AAV-shCAND1) were performed to evaluate the therapeutic efficacy of targeting CAND1. RNA-Seq and lipidomic assays followed by serial biochemical experiments including mass spectrometry, immunoprecipitation and GST pull-down were performed to dissect the underlying mechanisms. CAND1 promoted the expression of lipid synthesis genes by disrupting SCF complex assembly and lipid accumulation. Furthermore, we identified hnRNPA2B1 as a novel F-box protein 11 (FBXO11)-binding partner. FBXO11 directly bound to hnRNPA2B1 and promoted hnRNPA2B1 ubiquitination and subsequent degradation. Our evaluations of the therapeutic efficacy of AAV-shCAND1 injections confirmed that targeting the CAND1-SCF -hnRNPA2B1A signalling axis was therapeutically effective. CAND1 downregulation significantly reduced the tumour burden in a primary mouse liver cancer model and a PDX model. Our results highlight that CAND1 is associated with poor prognosis in HCC and regulates lipid metabolic reprogramming by dissociating the SCF complex. Targeting the CAND1-SCF -hnRNPA2B1 axis may be a novel strategy for HCC treatment.

[This corrects the article DOI: 10.7150/ijbs.69495.].

P237; 巡视器导航相机在发射前已完成标定,但在飞抵行星表面开展工作前需经过长时间飞行,其间受到的外力可能导致相机参数发生变化,所以在着陆后需要对导航双目相机重新标定.本文首先介绍了以太阳能电池板为标定板,然后通过Hough变换、聚类思想和最小二乘直线拟合法提取出电池板格网线,根据直线参数重新标定导航双目相机外参的标定方法,最后进行了两项试验.试验1以嫦娥4号影像进行格网线提取试验,并与传统的Hough变换直线提取结果进行比较,本文提取方法更准确;试验2以模拟直线参数进行双目相机外参标定试验,结果说明解算精度较高,方法可行有效.但该相机标定方法将相机内参作为已知值,并单独解算左、右相机外参,下一步将继续研究相机内、外参同时标定的方法和双目相机一步标定的方法.