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Hanbing Yang,1 Wenjing Zhang,2 Qingxia Luan,3 Yanchao Liu2 1Department of Interventional Thoracic Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of China; 2Department of Hematology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of ChinaCorrespondence: Hanbing YangDepartment of Interventional Thoracic Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of ChinaTel +86-0536-3081293Email yanghb3240@163.comPurpose: MicroRNA-4284 (miR-4284) was demonstrated to be aberrantly expressed and affected cell activities in some types of diseases, including cancer. However, the role of miR-4284 in non-small cell lung cancer (NSCLC) is largely unknown. The aim of this study was to investigate the expression and biological role of miR-4284 in NSCLC.Patients and Methods: The qRT-PCR assay was applied to detect the expression of miR-4284 in NSCLC tissues and cell lines. Kaplan–Meier curve method and multiple Cox regression analyses were used to explore the prognostic factors for postoperative NSCLC patients. The CCK-8 assay was carried out to measure the proliferative abilities of A549 and H1299 cells. Transwell migration and invasion assays were used to determine the cell migratory and invasive capabilities of NSCLC cells.Results: miR-4284 expression was upregulated in NSCLC tissues and cell lines. High expression of miR-4284 was correlated with poor differentiation, positive lymph node metastasis, and advanced TNM stages. In addition, postoperative patients with higher expression of miR-4284 exhibited a shorter overall survival time than those with lower expression of miR-4284. Moreover, the upregulation of miR-4284 accelerated cell proliferative, migratory, and invasive abilities of A549 and H1299 cells, while the downregulation of miR-4284 inhibited these cellular capabilities.Conclusion: miR-4284 was noticeably upregulated in NSCLC and associated with a poor prognosis of postoperative NSCLC patients. miR-4284 promoted the proliferation, migration, and invasion of A549 and H1299 cells. This study indicated that miR-4284 might serve as a prognostic biomarker and a potential therapeutic target for postoperative NSCLC patients.Keywords: miR-4284, malignant activities, non-small cell lung cancer, prognosis, biomarker

Background: At present, due to the heterogeneity of breast cancer, common tumor markers have certain limitations in clinical prognostic evaluation. This suggests an unmet need for markers to predict clinical outcomes and potentially guide targeted therapies. The present study sought to explore the expression level and clinical significance of undifferentiated embryonic cell transcription factor 1 (UTF1) in breast cancer., Methods: Immunohistochemistry (IHC) was used to detect the expression of UTF1 in 221 breast cancer samples. The clinical significance of UTF1 protein expression in breast cancer tissues was evaluated by combining clinicopathological parameters and UTF1 expression profile. We performed 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays to evaluate the effect of UTF1 on Bcap37 cell proliferation. Wound healing assay and transwell migration assay were used to evaluate the changes of cell invasion and migration ability, respectively. All experiments were performed with 3 biological replicates. Genomic differences after UTF1 overexpression were evaluated by RNA sequencing technology and the possible functions and regulatory mechanisms were elucidated., Results: The findings showed that UTF1 expression level was significantly correlated with tumor size (P=0.004), but not with patient age, tumor histological stage, lymph node metastasis, as well as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki67 expression levels. Kaplan-Meier survival analysis and Cox proportional hazard model indicated that UTF1 expression was significantly associated with overall survival (OS) time of breast cancer patients. The median survival time of patients with high expression level of UTF1 was shorter compared with that of patients with low UTF1 expression level. The results of cell experiments showed that UTF1 overexpression could significantly promote the growth, proliferation, migration, and invasion of breast cancer cells. The RNA sequencing results showed that UTF1 was not only closely related to apoptosis genes, but also closely related to the nuclear factor (NF)-kappa B pathway., Conclusions: The findings of the current study indicate that UTF1 is involved in occurrence and tumor progression and is significantly associated with prognosis of breast cancer patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2890/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC). In this study, ENKUR expression in HCC tissue and cells were detected. The relationship between ENKUR expression and clinical pathology was also assessed. In vivo and in vitro experiments were conducted to explore the effects and molecular basis of ENKUR and CB in HCC. ENKUR expression was correlated with HCC progression and patient prognosis. Furthermore, ENKUR could inhibit tumor proliferation, metastasis, and sorafenib resistance in HCC. Mechanistic studies showed that ENKUR or its Enkurin domain could bind to MYH9 and decrease its expression by binding to β-catenin and inhibiting its nuclear transfer, thus decreasing c-Jun level. Low expression of MYH9 suppressed recruitment of deubiquitination enzyme USP7, promoting degradation of the c-Myc. Therefore, cell cycle and EMT signals were suppressed. CB as a safe and effective anti-cancer compound up-regulates the expression of ENKUR via inhibiting PI3K/AKT/c-Jun-mediated transcription suppression. These findings show that ENKUR induced by CB antagonizes β-catenin/c-Jun/MYH9/USP7 pathway, thus increasing c-Myc ubiquitin degradation and finally suppressing cell cycle and EMT signals., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)