{"title":"Nuclear miRNAs as transcriptional regulators in processes related to various cancers (Review).","authors":"Ziqiang Wang, Yu Zhang, Kun Li","doi":"10.3892/ijo.2024.5644","DOIUrl":"https://doi.org/10.3892/ijo.2024.5644","url":null,"abstract":"MicroRNAs (miRNAs) are noncoding small nucleic acids that contain ~22 nucleotides and are considered to promote the degradation or inhibit the translation of mRNA by targeting its 3'‑untranslated region. However, growing evidence has revealed that nuclear miRNAs, combined with gene promoters or enhancers, are able to directly mediate gene transcription. These miRNAs exert a critical influence on cancer progression by affecting cell growth, migration and invasion. In this review, the direct regulation of gene expression by nuclear miRNAs at the transcriptional level was discussed and summarized, and their mechanisms of action in cancers were highlighted with reference to the various body systems.","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"214 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giulia Tedesco, Manuela Santarosa, Roberta Maestro
{"title":"Beyond self‑eating: Emerging autophagy‑independent functions for the autophagy molecules in cancer (Review).","authors":"Giulia Tedesco, Manuela Santarosa, Roberta Maestro","doi":"10.3892/ijo.2024.5645","DOIUrl":"https://doi.org/10.3892/ijo.2024.5645","url":null,"abstract":"Autophagy is a conserved catabolic process that controls organelle quality, removes misfolded or abnormally aggregated proteins and is part of the defense mechanisms against intracellular pathogens. Autophagy contributes to the suppression of tumor initiation by promoting genome stability, cellular integrity, redox balance and proteostasis. On the other hand, once a tumor is established, autophagy can support cancer cell survival and promote epithelial‑to‑mesenchymal transition. A growing number of molecules involved in autophagy have been identified. In addition to their key canonical activity, several of these molecules, such as ATG5, ATG12 and Beclin‑1, also exert autophagy‑independent functions in a variety of biological processes. The present review aimed to summarize autophagy‑independent functions of molecules of the autophagy machinery and how the activity of these molecules can influence signaling pathways that are deregulated in cancer progression.","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"39 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Heterogeneity of primary and metastatic CAFs: From differential treatment outcomes to treatment opportunities (Review).","authors":"Zixing Kou, Cun Liu, Wenfeng Zhang, Changgang Sun, Lijuan Liu, Qiming Zhang","doi":"10.3892/ijo.2024.5642","DOIUrl":"https://doi.org/10.3892/ijo.2024.5642","url":null,"abstract":"Compared with primary tumor sites, metastatic sites appear more resistant to treatments and respond differently to the treatment regimen. It may be due to the heterogeneity in the microenvironment between metastatic sites and primary tumors. Cancer‑associated fibroblasts (CAFs) are widely present in the tumor stroma as key components of the tumor microenvironment. Primary tumor CAFs (pCAFs) and metastatic CAFs (mCAFs) are heterogeneous in terms of source, activation mode, markers and functional phenotypes. They can shape the tumor microenvironment according to organ, showing heterogeneity between primary tumors and metastases, which may affect the sensitivity of these sites to treatment. It was hypothesized that understanding the heterogeneity between pCAFs and mCAFs can provide a glimpse into the difference in treatment outcomes, providing new ideas for improving the rate of metastasis control in various cancers.","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"290 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway.","authors":"Pengren Luo, Jinhong Yang, Lipeng Jian, Jigen Dong, Shi Yin, Chao Luo, Shuai Zhou","doi":"10.3892/ijo.2024.5643","DOIUrl":"https://doi.org/10.3892/ijo.2024.5643","url":null,"abstract":"Glioma is the most common type of primary intracranial malignant tumor, and because of its high invasiveness and recurrence, its prognosis remains poor. The present study investigated the biological function of piggyBac transportable element derived 5 (PGBD5) in glioma. Glioma and para-cancerous tissues were obtained from five patients. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of PGBD5. Transwell assay and flow cytometry were used to evaluate cell migration, invasion, apoptosis and cell cycle distribution. In addition, a nude mouse tumor transplantation model was established to study the downstream pathways of PGBD5 and the molecular mechanism was analyzed using transcriptome sequencing. The mRNA and protein expression levels of PGBD5 were increased in glioma tissues and cells. Notably, knockdown of PGBD5 <i>in vitro</i> could inhibit the migration and invasion of glioma cells. In addition, the knockdown of PGBD5 expression promoted apoptosis and caused cell cycle arrest in the G<sub>2</sub>/M phase, thus inhibiting cell proliferation. Furthermore, <i>in vivo</i> experiments revealed that knockdown of PGBD5 expression could inhibit Ki67 expression and slow tumor growth. Changes in PGBD5 expression were also shown to be closely related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In conclusion, interference with PGBD5 could inhibit the malignant progression of glioma through the PPAR pathway, suggesting that PGBD5 may be a potential molecular target of glioma.","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).","authors":"Tianyu Wang, Xiaobing Li, Ruijie Ma, Jian Sun, Shuhong Huang, Zhigang Sun, Meng Wang","doi":"10.3892/ijo.2024.5627","DOIUrl":"10.3892/ijo.2024.5627","url":null,"abstract":"<p><p>Neddylation, akin to ubiquitination, represents a post‑translational modification of proteins wherein neural precursor cell‑expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8‑mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti‑CRC target.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"64 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Xenograft and organoid models in developing precision medicine for gastric cancer (Review).","authors":"Jiao Xu, Bixin Yu, Fan Wang, Jin Yang","doi":"10.3892/ijo.2024.5629","DOIUrl":"10.3892/ijo.2024.5629","url":null,"abstract":"<p><p>Gastric cancer (GC), a highly heterogeneous disease, has diverse histological and molecular subtypes. For precision medicine, well‑characterized models encompassing the full spectrum of subtypes are necessary. Patient‑derived tumor xenografts and organoids serve as important preclinical models in GC research. The main advantage of these models is the retention of phenotypic and genotypic heterogeneity present in parental tumor tissues. Utilizing diverse sequencing techniques and preclinical models for GC research facilitates accuracy in predicting personalized clinical responses to anti‑cancer treatments. The present review summarizes the latest advances of these two preclinical models in GC treatment and drug response assessment.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"64 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HER2<sup>+</sup> advanced gastric cancer: Current state and opportunities (Review).","authors":"Hui-Hui Hu, Sai-Qi Wang, Huichen Zhao, Zhe-Sheng Chen, Xiaojing Shi, Xiao-Bing Chen","doi":"10.3892/ijo.2024.5624","DOIUrl":"10.3892/ijo.2024.5624","url":null,"abstract":"<p><p>Human epidermal growth factor receptor 2 (HER2)<sup>+</sup> gastric cancer (GC) is a distinct subtype of GC, accounting for 10‑20% of all cases of GC. Although the development of the anti‑HER2 monoclonal antibody trastuzumab has markedly improved response rates and prognosis of patients with HER2<sup>+</sup> advanced GC (AGC), drug resistance remains a considerable challenge. Therefore, dynamic monitoring of HER2 expression levels can facilitate the identification of patients who may benefit from targeted therapy. Besides trastuzumab, DS‑8201 and RC48 have been applied in the treatment of HER2<sup>+</sup> AGC, and several novel anti‑HER2 therapies are undergoing preclinical/clinical trials. At present, combination immunotherapy with anti‑HER2 agents is used as the first‑line treatment of this disease subtype. New promising approaches such as chimeric antigen receptor T‑cell immunotherapy and cancer vaccines are also being investigated for their potential to improve clinical outcomes. The current review provides new insights that will guide the future application of anti‑HER2 therapy by summarizing research progress on targeted therapy drugs for HER2<sup>+</sup> AGC and combination treatments.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"64 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinzhe Sun, Shiqian Chen, Dan Zang, Hetian Sun, Yan Sun, Jun Chen
{"title":"Butyrate as a promising therapeutic target in cancer: From pathogenesis to clinic (Review).","authors":"Jinzhe Sun, Shiqian Chen, Dan Zang, Hetian Sun, Yan Sun, Jun Chen","doi":"10.3892/ijo.2024.5632","DOIUrl":"10.3892/ijo.2024.5632","url":null,"abstract":"<p><p>Cancer is one of the leading causes of mortality worldwide. The etiology of cancer has not been fully elucidated yet, and further enhancements are necessary to optimize therapeutic efficacy. Butyrate, a short‑chain fatty acid, is generated through gut microbial fermentation of dietary fiber. Studies have unveiled the relevance of butyrate in malignant neoplasms, and a comprehensive understanding of its role in cancer is imperative for realizing its full potential in oncological treatment. Its full antineoplastic effects via the activation of G protein‑coupled receptors and the inhibition of histone deacetylases have been also confirmed. However, the underlying mechanistic details remain unclear. The present study aimed to review the involvement of butyrate in carcinogenesis and its molecular mechanisms, with a particular emphasis on its association with the efficacy of tumor immunotherapy, as well as discussing relevant clinical studies on butyrate as a therapeutic target for neoplastic diseases to provide new insights into cancer treatment.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"64 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sujuan Li, Sen Wang, Anping Zhang, Lixia Luo, Jie Song, Guoli Wei, Zhijun Fang
{"title":"Cucurbitacin IIa promotes the immunogenic cell death‑inducing effect of doxorubicin and modulates immune microenvironment in liver cancer.","authors":"Sujuan Li, Sen Wang, Anping Zhang, Lixia Luo, Jie Song, Guoli Wei, Zhijun Fang","doi":"10.3892/ijo.2024.5625","DOIUrl":"10.3892/ijo.2024.5625","url":null,"abstract":"<p><p>The immunogenic cell death (ICD) has aroused great interest in cancer immunotherapy. Doxorubicin (DOX), which can induce ICD, is a widely used chemotherapeutic drug in liver cancer. However, DOX‑induced ICD is not potent enough to initiate a satisfactory immune response. Cucurbitacin IIa (CUIIa), a tetracyclic triterpene, is a biologically active compound present in the <i>Cucurbitaceae</i> family. The present study assessed the effects of the combination of DOX and CUIIa on the viability, colony formation, apoptosis and cell cycle of HepG2 cells. <i>In vivo</i> anticancer effect was performed in mice bearing H22 tumor xenografts. The hallmark expression of ICD was tested using immunofluorescence and an ATP assay kit. The immune microenvironment was analyzed using flow cytometry. The combination of CUIIa and DOX displayed potent apoptosis inducing, cell cycle arresting and <i>in vivo</i> anticancer effects, along with attenuated cardiotoxicity in H22 mice. The combination of DOX and CUIIa also facilitated ICD as manifested by elevated high‑mobility group box 1, calreticulin and ATP secretion. This combination provoked a stronger immune response in H22 mice, including dendritic cell activation, increment of cytotoxic T cells and T helper 1 cells. Moreover, the proportion of immunosuppressive cells including myeloid‑derived suppressor cells, T regulatory cells and M2‑polarized macrophages, decreased. These data suggested that CUIIa is a promising combination partner with DOX for liver cancer treatment, probably via triggering ICD and remolding the immune microenvironment.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"64 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria G Kakafika, Areti A Lyta, George I Gavriilidis, Stefanos A Tsiftsoglou, Androulla N Miliotou, Ioannis S Pappas, Ioannis S Vizirianakis, Lefkothea C Papadopoulou, Asterios S Tsiftsoglou
{"title":"Targeting mitochondrial bioenergetics by combination treatment with imatinib and dichloroacetate in human erythroleukemic K‑562 and colorectal HCT‑116 cancer cells.","authors":"Maria G Kakafika, Areti A Lyta, George I Gavriilidis, Stefanos A Tsiftsoglou, Androulla N Miliotou, Ioannis S Pappas, Ioannis S Vizirianakis, Lefkothea C Papadopoulou, Asterios S Tsiftsoglou","doi":"10.3892/ijo.2024.5630","DOIUrl":"10.3892/ijo.2024.5630","url":null,"abstract":"<p><p>Tumor malignant cells are characterized by dysregulation of mitochondrial bioenergetics due to the 'Warburg effect'. In the present study, this metabolic imbalance was explored as a potential target for novel cancer chemotherapy. Imatinib (IM) downregulates the expression levels of <i>SCΟ2</i> and <i>FRATAXIN</i> (<i>FXN</i>) genes involved in the heme‑dependent cytochrome <i>c</i> oxidase biosynthesis and assembly pathway in human erythroleukemic IM‑sensitive K‑562 chronic myeloid leukemia cells (K‑562). In the present study, it was investigated whether the treatment of cancer cells with IM (an inhibitor of oxidative phosphorylation) separately, or together with dichloroacetate (DCA) (an inhibitor of glycolysis), can inhibit cell proliferation or cause death. Human K‑562 and IM‑chemoresistant K‑562 chronic myeloid leukemia cells (K‑562R), as well as human colorectal carcinoma cells HCT‑116 (+/+p53) and (‑/‑p53, with double <i>TP53</i> knock-in disruptions), were employed. Treatments of these cells with either IM (1 or 2 µM) and/or DCA (4 mΜ) were also assessed for the levels of several process biomarkers including SCO2, FXN, lactate dehydrogenase A, glyceraldehyde‑3‑phosphate dehydrogenase, pyruvate kinase M2, hypoxia inducing factor‑1a, heme oxygenase‑1, NF‑κB, stem cell factor and vascular endothelial growth factor via western blot analysis. Computational network biology models were also applied to reveal the connections between the ten proteins examined. Combination treatment of IM with DCA caused extensive cell death (>75%) in K‑562 and considerable (>45%) in HCT‑116 (+/+p53) cultures, but less in K‑562R and HCT‑116 (‑/‑p53), with the latter deficient in full length p53 protein. Such treatment, markedly reduced reactive oxygen species levels, as measured by flow‑cytometry, in K‑562 cells and affected the oxidative phosphorylation and glycolytic biomarkers in all lines examined. These findings indicated, that targeting of cancer mitochondrial bioenergetics with such a combination treatment was very effective, although chemoresistance to IM in leukemia and the absence of a full length p53 in colorectal cells affected its impact.</p>","PeriodicalId":14175,"journal":{"name":"International journal of oncology","volume":"64 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}