International journal of oncology最新文献

Solute carrier family 25 member 1 (SLC25A1) affects lipid metabolism and energy regulation in multiple types of tumor cell, affecting their proliferation and survival. To the best of our knowledge, however, the impact of SLC25A1 on the proliferation and survival of esophageal squamous cell carcinoma (ESCC) cells has yet to be explored. Here, SLC25A1 expression was detected in ESCC tissues and cell lines. SLC25A1 was silenced or blocked by lentivirus transfection or 2‑[(4‑chloro‑3‑nitrophenyl)sulfonylamino]benzoic acid in ESCC cells. To evaluate the impact of SLC25A1 on in vivo and in vitro proliferation, invasion and migration of ESCC cells, Cell Counting‑Kit, wound healing, colony formation, Transwell, EdU, flow cytometry, tumor xenograft in nude mice, lipid metabolism and energy metabolism detection assays were performed. Reverse transcription‑quantitative PCR and western blot analysis were performed to determine expression of downstream molecules and pathway proteins following the silencing and blockade of SLC25A1. SLC25A1 was significantly overexpressed in ESCC tissue and cell lines. The targeted silencing of SLC25A1 or inhibition of its protein led to a significant decrease in proliferative, invasive and migratory capabilities of ESCC cells, accompanied by increased apoptosis. Additionally, silencing of the SLC25A1 gene significantly inhibited xenograft tumor growth in vivo. The present results indicate that knockdown or blockade of SLC25A1 can significantly impede the malignant biological behavior of ESCC.

Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation in the bone marrow (BM). Previously, it was reported that G‑protein‑coupled receptor 4 (LGR4) contributed to early hematopoiesis and was associated with poor prognosis in patients with MM. However, the mechanism of cell homing and migration, which is critical for MM progression, remains unclear. In the present study, cell counting, cell cycle and BrdU assays were performed to evaluate cell proliferation. Transwell assay and Xenograft mouse models were performed to evaluate cell migration and homing ability both in vitro and in vivo. I was found that overexpression of LGR4 promotes MM cell adhesion, migration and homing to BM both in vitro, while exacerbating osteolytic bone destruction in vivo. However, the LGR4 knockdown displayed the opposite effect. Further mechanistic studies demonstrated that LGR4 activated the nuclear factor kappa B (NF‑κB) signaling pathway and migration‑related adhesion molecule, thus promoting MM cell homing. Moreover, inhibiting the NF‑κB pathway was found to suppress MM cell homing. These findings identify LGR4 as a critical regulator of myeloma cell migration, homing and tumorigenesis, offering a potential therapeutic strategy for MM treatment.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the western blot assay data shown in Fig. 4G on p. 717 were strikingly similar to data that had appeared in a paper published previously in the journal Molecular Cancer Therapeutics, which had been written by different authors at different research institutes. Moreover, there appeared to be as many as five sets of duplicated protein bands in Fig. 4B and C, including the appearance of apparently the same protein band in different orientations in Fig. 4C in one case, and certain data shown in Fig. 4B and G had apparently been re-used in these figure parts. After having performed an independent assessment of these issues in the Editorial Office, these concerns of the reader were found to have been validated; therefore, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The corresponding author, Claudio Festuccia, takes full responsibility for the raised concerns and clarifies that the other co-authors were not directly involved in the preparation of the submitted figures. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 40: 711-720, 2012; DOI: 10.3892/ijo.2011.1270].

Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in PI3KCA, loss of PTEN or activation of receptor tyrosine kinases. In HPV‑negative tumors, CDKN2A (encoding p16 protein) inactivation or CCND1 (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines. Inhibitor efficacy was assessed in vitro using MTT assay and western blotting analysis. Cell cycle analysis was performed using flow cytometry and apoptosis was assessed using annexin V staining. Metabolic changes in terms of glycolysis and oxidative metabolism were measured by Seahorse XF96 extracellular Flux analysis. The results of the present study showed that both HPV‑positive and ‑negative HNSCC cell lines were sensitive to PI3Ki. In general, PI3Ki decreased PI3K/Akt/mTOR pathway activity, resulting in apoptosis, and decreased oxidative and glycolytic metabolism. The CDKi were particularly effective in blocking HPV‑negative cell line viability, showing decreased retinoblastoma expression and G1‑phase cell cycle arrest, whereas apoptosis was not induced. Thus, PI3Ki and CDKi efficiently inhibited their respective pathways and HNSCC cell viability in vitro, with the latter occurring only in HPV‑negative cell lines. Whereas PI3Ki induced apoptosis and attenuated cellular metabolism, CDKi led to cell cycle arrest. Further research should be performed to elucidate whether (a combination of) these inhibitors may be effective therapeutic agents for patients with HNSCC.

Angiopoietin‑like 4 (ANGPTL4), a member of the angiopoietin family, plays critical roles in angiogenesis, lipid metabolism and inflammation. It has been demonstrated that ANGPTL4 has significant influence on various diseases. Accumulating evidence has highlighted the impacts of ANGPTL4 on human malignancies. ANGPTL4 is commonly overexpressed in various types of cancer, such as breast, non‑small cell lung, gastric and colorectal cancer. Its upregulation promotes tumor growth, invasion, metastasis and angiogenesis, as well as metabolic reprogramming and resistance to programmed cell death, radiotherapy and chemotherapy. However, ANGPTL4 has also exhibited antitumor effects under certain conditions, indicating its complex roles in tumor biology. The transcriptional regulation of ANGPTL4 is influenced by multiple factors, such as HIF‑1, PPARs, TGF‑β and long non‑coding RNAs. In terms of signaling pathways, STATs, PI3K/AKT and COX-2/PGE2 are important in regulating cellular processes. The present review summarizes the biological functions of ANGPTL4 in tumors and its association with patient prognosis. Furthermore, the key molecular mechanisms and potential reasons for its dual roles in cancer are also discussed. In conclusion, ANGPTL4 is a valuable diagnostic biomarker and a potential therapeutic target for human cancers.

Circular (circ)RNAs participate in colorectal cancer (CRC) occurrence and progression. However, the role of hsa_circ_0004662 (circ_0004662) in CRC remains unknown. Reverse transcription‑quantitative PCR noted high expression of circ_0004662 in CRC compared with normal colorectal epithelial cells. circ_0004662 knockdown inhibited migration of CRC cells in vitro and in vivo; would healing and Transwell assays showed that circ_0004662 overexpression contributed to CRC migration. Nuclear cytoplasmic analysis and fluorescence in situ hybridization revealed localization of circ_0004662 in the nucleus and cytoplasm. CircRNADB databases predicted that circ_0004662 exhibited translational potential and liquid chromatography‑mass spectrometry (LC‑MS) of circ_0004662 pull‑down products suggested that circ_0004662 bound to multiple ribosomal subunits. However, peptide products of 149aa translated by circ_0004662, with a molecular weight of ~17 kDa were not detected. Nevertheless, LC‑MS analysis indicated that circ_0004662 bound multiple proteins. Immunoprecipitation of RNA‑binding proteins revealed that circ_0004662 bound to heterogeneous nuclear ribonucleoprotein M (hnRNPM) and that hnRNPM interference decreased circ_0004662 expression, thereby affecting CRC progression. In summary, circ_0004662 was significantly upregulated in CRC. As a non‑coding RNA, it may promote CRC progression by binding to hnRNPM, which may serve as a potential target for treating CRC.

Plexiform neurofibromas (PNFs) are benign tumors that affect 20‑50% of patients with type I neurofibromatosis (NF1). PNF carries a risk of malignancy. There is no effective cure for PNF. Its onset may be associated with genetic and metabolic abnormalities, but the exact mechanisms remain unclear. Succinate‑CoA ligase GDP/ADP‑Forming Subunit α(SUCLG1), a catalytic enzyme in the tricarboxylic acid cycle, is highly expressed in PNF. The present study aimed to explore the role of SUCLG1 in function and metabolism of PNF cells. SUCLG1 expression was verified using western blotting and immunofluorescence. After inducing SUCLG1 knockdown and overexpression, functional changes in PNF cells were assessed, as well as effects of SUCLG1 on cell respiration and glucose metabolism. Quantitative PCR, WB, electron microscopy and Flow cytometry demonstrated that SUCLG1 enhanced mitochondrial quality and promoted mitochondrial fusion, thereby driving proliferation and migration of tumor cells, inhibiting apoptosis and altering the cell cycle. A Seahorse assay showed that elevated SUCLG1 expression enhanced cell aerobic respiration without affecting the glycolytic process. This suggests that SUCLG1 upregulation in PNF does not trigger the Warburg effect associated with malignant tumors. This study also demonstrated the positive regulation of cellular function by promoting the expression level of the SLC25A1 gene when SUCLG1 expression was elevated. In conclusion, SUCLG1 altered the mechanism of mitochondrial quality control to enhance cell aerobic respiration, thereby driving the pathogenesis of PNF. Thus, SUCLG1 can serve as a potential target in future therapeutic strategies.

Following the publication of this article, a concerned reader drew to the Editor's attention that there appeared to be the duplication of a pair of western blots in each of Figs. 4 and 6, with the possibility of the bands in question having been resized in one of these cases. After having conducted an internal investigation, the Editorial Office also determined that there was a further instance of duplication of western bands comparing between Figs. 2 and 4. In all cases, the bands that had been re‑used were intended to show the results of differently performed experiments. After assessing the issues that have come to light with regard to the duplications of western blots in this paper, in view of the apparently misassembled data that has been identified in each of Figs. 2, 4 and 6, the Editor of International Journal of Oncology has determined that this paper should be retracted from the publication on the grounds of a lack of confidence in the presented data. Upon contacting the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused, and we also thank the reader for bringing this matter to our attention. [International Journal of Oncology 43: 919‑926, 2013; DOI: 10.3892/ijo.2013.2008].

Breast cancer (BC) continues to be the leading cause of cancer‑related mortality among women, placing a substantial disease burden on the global female population. MicroRNAs (miRNAs) are members of a large class of non‑coding RNAs capable of regulating gene expression at the post‑transcriptional level. With cases of early‑onset BC on the rise, miRNAs are promising biomarkers and therapeutic targets for early BC detection and treatment. Dysregulated miRNA expression is known to be closely linked to BC development and metastasis in cancer cells via metabolic reprogramming. Normal cellular metabolism is tightly regulated by various complex signaling pathways. Therefore, dysregulation of metabolism due to metabolic reprogramming is considered a hallmark of cancer. The present review delves into the crucial roles that miRNAs serve in disordered cellular metabolism of BC by targeting gene transcripts, key metabolic enzymes and transporter proteins responsible for regulating major cellular metabolism pathways. The future outlook and clinical implications of miRNAs as potential diagnostic, prognostic and therapeutic markers in BC metabolism are also discussed.

Cancer poses a significant global health challenge and its progression is intricately connected to the interplay among various cell types and molecular pathways. In recent years, research has focused on the roles of vascular endothelial cells (VECs) and exosomes within the tumor microenvironment. Anomalies in tumor vascular integrity and function create a conducive milieu for cancer cell proliferation. Despite efforts in clinical anti‑angiogenic interventions, the anticipated outcomes remain elusive. VECs have the capability to transition into mesenchymal cells through endothelial‑to‑mesenchymal transition, thereby affecting cancer advancement. Exosomes are minute membrane‑bound vesicles generated by cells, serving as vital extracellular elements that facilitate cell‑to‑cell communication. They participate in modulating the tumor microenvironment, thereby influencing tumor progression, metastasis, drug resistance and angiogenesis. Additionally, exosomes serve as efficient carriers for drug delivery, as well as targeting and suppressing tumor cells. In summary, understanding the intricate and interconnected mechanisms of VECs and exosomes in cancer, encompassing tumor angiogenesis, microenvironment modulation and immune regulation, is crucial. A comprehensive exploration of these mechanisms may provide insight into cancer treatment and prevention and yield novel therapeutic targets.