Oncology reports最新文献

N6‑methyladenosine (m⁶A) is the predominant chemical modification of eukaryotic mRNA, dynamically mediated by the RNA methyltransferase, methyltransferase-like 3 (METTL3). m⁶A modification plays a critical role in cancer progression through post‑transcriptional regulation in various types of cancer. However, the role of METTL3 and its associated m⁶A modification in colorectal tumorigenesis remains to be fully elucidated. In the present study, it was demonstrated that METTL3 expression and the m⁶A levels were both upregulated in colorectal cancer (CRC) and positively associated with clinical progression, based on the bioinformatics analysis of cancer databases. Furthermore, knockdown and overexpression of METTL3 notably affected CRC cell viability, apoptosis and migration in vitro. Similarly, xenograft animal models confirmed that METTL3 promoted CRC tumorigenicity in vivo. Mechanistically, it was revealed that the m⁶A modification of matrix metallopeptidase 9 (MMP9) mRNA mediated by METTL3 promoted its expression in CRC by decreasing its degradation. Collectively, the findings of the present study suggested that the METTL3/MMP9 axis could serve as a novel promising therapeutic candidate for CRC.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that there appeared to be overlapping sections of data in the three Transwell invasion assay images shown in Fig. 4A, and in the 3D sphere formation assay data shown in Fig. 5, on p. 2068; moreover, certain of the data featured in one of the data panels in Fig. 4A also appeared in a subsequent publication by the same research group in the journal Scientific Reports. The authors requested the publication of a corrigendum to acount for the errors made in assembling the data in Figs. 4 and 5; however, after careful consideration of the matter, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal on account of the number of issues that were identified, and a general lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 43: 2062‑2072, 2020; DOI: 10.3892/or.2020.7549].

Bladder cancer is the most common malignant tumor of the urinary system with high morbidity and no clear pathogenesis. The Hippo signaling pathway is an evolutionarily conserved pathway that regulates organ size and maintains tissue homeostasis. Yes‑associated protein 1 (YAP1) is a key effector of this pathway and regulates downstream target genes by binding to transcriptional co‑activators with PDZ binding sequences (TAZ). Several studies have demonstrated that YAP1 is overexpressed in bladder cancer and is involved in adverse outcomes such as bladder cancer occurrence, progression, resistance to cisplatin and the recurrence of tumours. The present review summarized the involvement of YAP1 in bladder cancer disease onset and progression, and the mechanism of YAP1 involvement in bladder cancer treatment. In addition, this study further explored the potential of YAP1 in the diagnosis and treatment of bladder cancer. This study aimed to explore the potential mechanism of YAP1 in the treatment of bladder cancer.

Thyroid carcinoma (TC) represents the most prevalent malignancy of the endocrine system. Protein arginine methyltransferase 1 (PRMT1) is a critical member of the protein arginine methyltransferase family in mammals and is involved in multiple biological processes. This study aimed to investigate the function of PRMT1 in TC. In the present study, human TC cell lines (8505C, CAL62, and BCPAP) and a normal human thyroid cell line Nthy‑ori 3‑1 were employed. Small interfering RNA targeting PRMT1 was used to knock down PRMT1 expression in 8505C cells, and PRMT1 overexpression plasmids were transfected into BCPAP cells. Cell viability was assessed using a CCK‑8 and colony formation assays. Apoptosis was measured using flow cytometry and TUNEL assays. Cell migration was assessed using wound healing and Transwell assays. Reverse transcription‑quantitative PCR was used to determine the mRNA expression levels of PRMT1. Western blotting was used to detect the protein expression levels of PRMT1, E‑cadherin, vimentin, H4R3me2as, and zinc‑finger E homeobox‑binding 1 (ZEB1). Notably, PRMT1 expression was elevated in TC (P<0.01). PRMT1 knockdown inhibited TC cell proliferation and migration and concurrently enhanced migration. Furthermore, PRMT1 knockdown suppressed tumor growth and metastasis in a mouse model of TC. PRMT1 downregulation increased E‑cadherin expression and decreased the expression of vimentin, H4R3me2as, and ZEB1 in the TC cells and the mouse model of TC. Conversely, PRMT1 overexpression had the opposite effect on TC malignant characteristics (P<0.05). These findings suggest that PRMT1 knockdown inhibited TC malignancy by downregulating H4R3me2as/ZEB1, thereby highlighting novel therapeutic targets and diagnostic markers for the management of TC.

The treatment of advanced prostate cancer remains a formidable challenge due to the limited availability of effective treatment options. Therefore, it is imperative to identify promising druggable targets that provide substantial clinical benefits and to develop effective treatment strategies to overcome therapeutic resistance. Cyclosporin A (CsA) showed an anticancer effect on prostate cancer in cultured cell and xenograft models. E2F8 was identified as a master transcription factor that regulated a clinically significant CsA specific gene signature. The expression of E2F8 increased during prostate cancer progression and high levels of E2F8 expression are associated with a poor prognosis in patients with prostate cancer. MELK was identified as a crucial upstream regulator of E2F8 expression through the transcriptional regulatory network and Bayesian network analyses. Knockdown of E2F8 or MELK inhibited cell growth and colony formation in prostate cancer cells. High expression levels of E2F8 and androgen receptor (AR) are associated with a worse prognosis in patients with prostate cancer compared with low levels of both genes. The inhibition of E2F8 improved the response to AR blockade therapy. These results suggested that CsA has potential as an effective anticancer treatment for prostate cancer, while also revealing the oncogenic role of E2F8 and its association with clinical outcomes in prostate cancer. These results provided valuable insight into the development of therapeutic and diagnostic approaches for prostate cancer.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that a large number of data panels showing cell migration and invasion assay data in Figs. 3C and 5 contained overlapping sections, such that data that were intended to show results obtained under different experimental conditions may have been derived from a smaller number of original sources. In addition, certain of the data in this pair of figures were strikingly similar to data that were submitted for publication in another journal at around the same time as the above paper was submitted to Oncology Reports. Finally, regarding the western blotting data shown in Fig. 4B, an obvious splice in the gel strip was noticed for the FBXW7 bands, whereas no equivalent splice was present in the associated GADPH loading control, suggesting that these data originated from different gels. Owing to the fact that the contentious data in the above article were under consideration for publication at around the time that this was submitted to Oncology Reports, in addition the other features of concern regarding the data, the Editor has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 3030‑3038, 2017; DOI: 10.3892/or.2017.5995].

The heterogeneity of glioblastoma can suppress immune cell function and lead to immune evasion, which presents a challenge in developing effective molecular therapies for tumor cells. However, the study of tumor immune heterogeneity holds great potential for clinical immunotherapy. Liquid biopsy is a useful tool for accurately monitoring dynamic changes in tumor immune heterogeneity and the tumor microenvironment. This paper explores the heterogeneity of glioblastoma and the immune microenvironment, providing a therapeutic basis for individualized treatment. Using liquid biopsy technology as a new diagnostic method, innovative treatment strategies may be implemented for patients with glioblastoma to improve their outcomes.

T cells and natural killer (NK) cells are major effector cells recruited by cancer therapeutic bispecific antibodies; however, differences in the populations of these cells in individual tumors limit the general use of these antibodies. In the present study, trispecific antibodies were created, namely T cell and NK cell engagers (TaKEs), that recruit both T cells and NK cells. Notably, three Fc‑fused TaKEs were designed, TaKE1‑Fc, TaKE2‑Fc and TaKE3‑Fc, using variable fragments targeting the epidermal growth factor receptor on tumor cells, CD3 on T cells, and CD16 on NK cells. Among them, TaKE1‑Fc was predicted to form a circular tetrabody‑like configuration and exhibited the highest production and greatest cancer growth inhibitory effects. TaKE1 was prepared from TaKE1‑Fc by digesting the Fc region for further functional evaluation. The resulting TaKE1 exhibited trispecificity via its ability to bind cancer cells, T cells and NK cells, as well as comparable or greater cancer growth inhibitory effects to those of two bispecific antibodies that recruit T cells and NK cells, respectively. A functional trispecific antibody with the potential to exert strong therapeutic effects independent of T cell and NK cell populations was developed.

Lung adenocarcinoma (LUAD) poses a significant global health burden owing to its high incidence rate and unfavorable prognosis, driven by frequent recurrence and drug resistance. Understanding the biological mechanisms underlying LUAD is imperative to developing advanced therapeutic strategies. Recent research has highlighted the role of dysregulated microRNAs (miRNAs) in LUAD progression through diverse signaling pathways, including the Wnt and AKT pathways. Of particular interest is the novel pathological mechanism involving the interaction between competing endogenous RNAs (ceRNAs) and miRNAs. This review critically analyzed the impact of aberrant miRNA expression on LUAD development, shedding light on the associated signaling pathways. It also highlighted the emerging significance of ceRNA‑miRNA interactions in LUAD pathogenesis. Elucidating the intricate regulatory networks involving miRNAs and ceRNAs presents a promising avenue for the development of potential therapeutic interventions and diagnostic biomarkers in LUAD. Further research in this area is essential to advance precision medicine approaches and improve patient outcomes.

Acute myeloid leukemia (AML) is a common type of acute leukemia in adults and relapse is one of the main reasons for treatment failure. FLT3‑ITD mutations are associated with poor prognosis, short disease‑free progression survival and high relapse rates in patients with AML. STAT5 is activated by FLT3‑ITD and drives the pathogenesis of AML. STAT5 activation is usually a hallmark of hematologic malignancies and occurs in ~70% of patients with AML. Moreover, STAT5 is a key molecule which regulates hematopoiesis, and its high expression is closely associated with drug resistance, thus direct targeting of STAT5 for AML is of great clinical value. The present study introduces a new small‑molecule inhibitor that targets STAT5, presenting a promising approach for AML therapy. A high throughput fluorescence polarization (FP) screening system for STAT5 was designed and established, and used to screen an existing compound library to obtain the highly active small molecule inhibitor, topotecan hydrochloride. Topotecan hydrochloride was demonstrated to be an effective inhibitor of STAT5 by molecular docking prediction and cellular thermal shift assay. Topotecan hydrochloride bound to STAT5, inhibiting its dimerization, phosphorylation and transcription of specific target genes. The compound exhibits cellular activity at the nanomolar level and significantly inhibits the proliferation of human AML cell lines and FLT3‑ITD⁺ AML cells. Furthermore, topotecan hydrochloride has the potential to exert an anti‑tumor effect in vivo. Overall, topotecan hydrochloride offers a new opportunity for the treatment of AML and other hematologic malignancies by directly targeting STAT5.