Cancer Biology & Therapy最新文献

{"title":"Circ_RPPH1 facilitates progression of breast cancer via miR-1296-5p/TRIM14 axis.","authors":"Jing Jiang, Shenghong Shi, Wei Zhang, Chao Li, Long Sun, Qidong Ge, Xujun Li","doi":"10.1080/15384047.2024.2360768","DOIUrl":"10.1080/15384047.2024.2360768","url":null,"abstract":"<p><p><i>Circular RNA Ribonuclease P</i> <i>RNA Component H1</i> (<i>circ_RPPH1</i>) and microRNA (miRNA) <i>miR-1296-5p</i> play a crucial role in breast cancer (BC), but the molecular mechanism is vague. Evidence showed that <i>miR-1296-5p</i> can activate <i>tripartite motif-containing 14</i> (<i>TRIM14</i>). Clinical indications of eighty BC patients were collected and the <i>circ_RPPH1</i> expression was detected using real-time quantitative PCR. MCF-7 and MDA-MB-231 cells were transfected with overexpression or knockdown of <i>circ_RPPH1</i>, <i>miR-1296-5p</i>, or <i>TRIM14</i>. Cell counting kit-8, cell cloning formation, wound healing, Transwell, and flow cytometry assays were performed to investigate the malignant phenotype of BC. The dual-luciferase reporter gene analyses were applied to reveal the interaction between these target genes. Subcutaneous tumorigenic model mice were established with <i>circ_RPPH1</i> overexpression MDA-MB-231 cells in vivo; the tumor weight and volume, levels of <i>miR-1296-5</i> and <i>TRIM14</i> mRNA were measured. Western blot and immunohistochemistry were used to detect TRIM14 in cells and mice. <i>Circ_RPPH1</i> levels were notably higher in BC patients and have been found to promote cell proliferation, invasion, and migration of BC cells. <i>Circ_RPPH1</i> altered cell cycle and hindered apoptosis. <i>Circ_RPPH1</i> knockdown or <i>miR-1296-5p</i> overexpression inhibited the malignant phenotype of BC. Furthermore, <i>miR-1296-5p</i> knockdown reversed <i>circ_RPPH1</i>'s promotion effects on BC. Interestingly, <i>TRIM14</i> overexpression counteracts the inhibitory effects of <i>miR-1296-5p</i> overexpression and <i>circ_RPPH1</i> silencing on BC. Moreover, in BC tumor-bearing mice, <i>circ_RPPH1</i> overexpression led to increased TRIM14 expression and facilitated tumor growth. <i>Circ_RPPH1</i> enhanced BC progression through <i>miR-1296-5p</i>/<i>TRIM14</i> axis, indicating its potential as a biomarker and therapeutic target in BC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2360768"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma.","authors":"Xuewen Yang, Shisen Li, Chunsheng Xu, Shushang Liu, Xiang Zhang, Bo Lian, Mengbin Li","doi":"10.1080/15384047.2024.2365449","DOIUrl":"10.1080/15384047.2024.2365449","url":null,"abstract":"<p><p>We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced <i>in vivo</i> ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2365449"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-135b-5p promotes cetuximab resistance in colorectal cancer by regulating FOXN3.","authors":"Chun Peng, Xiaoqing Li, Yuhui Yao, Yu Nie, Lingyao Fan, Chuandong Zhu","doi":"10.1080/15384047.2024.2373497","DOIUrl":"10.1080/15384047.2024.2373497","url":null,"abstract":"<p><p>Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According to reports, the development of CRC is linked to miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between CRC tissues and adjacent tissues. However, it is unclear whether there is a correlation between miR-135b-5p and cetuximab (CTx) resistance in CRC. Use the GEO database to measure miR-135b-5p expression in CRC. Additionally, RT-qPCR was applied to ascertain the production level of miR-135b-5p in three human CRC cells and NCM460 cells. The capacity of cells to migrate and invade was examined utilizing the wound-healing and transwell assays, while the CCK-8 assay served for evaluating cell viability, as well as colony formation assays for proliferation. The expected target protein of miR-135b-5p in CRC cell cetuximab resistance has been investigated using western blot. Suppression of miR-135b-5p could increase the CTx sensitivity of CTx-resistant CRC cells, as manifested by the attenuation of proliferation, migration, and invasion ability. Mechanistic studies revealed miR-135b-5p regulates the epithelial-to-mesenchymal transition (EMT) process and Wnt/β-catenin signaling pathway through downgulating FOXN3. In short, knockdowning miR-135b-5p could increase FOXN3 expression in CRC cells, promote the EMT process, and simultaneously activate the Wnt/β-catenin signaling pathway to elevate CTx resistance in CRC cells.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2373497"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of pretreatment procalcitonin and neutrophil-lymphocyte ratio in extensive-stage small-cell lung cancer.","authors":"Dongfang Chen, Jianlin Xu, Yizhuo Zhao, Baohui Han, Runbo Zhong","doi":"10.1080/15384047.2024.2331273","DOIUrl":"10.1080/15384047.2024.2331273","url":null,"abstract":"<p><strong>Background: </strong>To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients.</p><p><strong>Method: </strong>A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤3.17), high NLR group (NLR＞3.17), low PCT group (PCT ≤0.06; ng/ml), high PCT group (PCT＞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS.</p><p><strong>Results: </strong>The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; <i>p</i> = .675). Patients with low pretreatment PCT (PCT ≤0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT＞0.06; ng/ml) (6.9 months vs 5.7 months; <i>p</i> = .043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (<i>p</i> ≤ .001) and pretreatment PCT (HR = 0.516; 95%CI 0.326-0.817; <i>p</i> = .005) were identified as independent factors associated with PFS.</p><p><strong>Conclusion: </strong>Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2331273"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140304969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer.","authors":"Jianqing Qiu, Ziyi Zhao, Hongyan Suo, Sarah E Paraghamian, Gabrielle M Hawkins, Wenchuan Sun, Xin Zhang, Tianran Hao, Beor Deng, Xiaochang Shen, Chunxiao Zhou, Victoria Bae-Jump","doi":"10.1080/15384047.2024.2325130","DOIUrl":"10.1080/15384047.2024.2325130","url":null,"abstract":"<p><p>Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of <i>Lkb1</i>^<i>fl/fl</i><i>p53</i>^<i>fl/fl</i> transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the <i>Lkb1</i>^<i>fl/fl</i><i>p53</i>^<i>fl/fl</i> mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2325130"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the apoptotic effect of Cabazitaxel and its pro-oxidant efficacy on the redox adaptation mechanisms in prostate cancer cells with different resistance phenotypes.","authors":"Isil Ezgi Eryilmaz, Unal Egeli, Gulsah Cecener","doi":"10.1080/15384047.2024.2329368","DOIUrl":"10.1080/15384047.2024.2329368","url":null,"abstract":"<p><p>Redox adaptation causes poor prognosis by adapting cancer cells to excessive oxidative stress. Previously, we introduced an oxidative stress-resistant metastatic prostate cancer (mPC) model (LNCaP-HPR) that redox adaptation reduced the effect of Cabazitaxel (Cab), the last taxane-derivative for metastatic castration-resistant PC (mCRPC). Whereas, we investigated for the first time whether there is an association between the altered apoptotic effect and pro-oxidant efficacy of Cab on the redox adaptation in PC cells with different phenotypes, including LNCaP mPC, LNCaP-HPR, C4-2 mCRPC, and RWPE-1 cells. Cab was shown pro-oxidant efficacy proportionally with the apoptotic effect, more prominent in the less aggressive LNCaP cells, by increasing the endogenous ROS, mitochondrial damage, and inhibiting nuclear ROS scavengers, p-Nrf2 and HIF-1α. However, the pro-oxidant and apoptotic effect was lower in the LNCaP-HPR and C4-2 cells, indicating that the drug sensitivity of the cells adapted to survive with more ROS was reduced via altered regulation of redox adaptation. Additionally, unlike LNCaP, Cab caused an increase in the p-NF-κB activation, suggesting that the p-NF-κB might accompany maintaining survival with the increased ROS in the aggressive PC cells. Moreover, the cytotoxic and apoptotic effects of Cab were less on RWPE-1 cells compared to LNCaP but were closer to those on the more aggressive LNCaP-HPR and C4-2 cells, except for the changing pro-oxidant effect of Cab. Consequently, this study indicates the variable pro-oxidant effects of Cab on redox-sensitive proteins, which could be a target for improving Cab's apoptotic effect more in aggressive PC cells.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2329368"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclophilin A: promising target in cancer therapy.","authors":"Shujuan Jin, Mengjiao Zhang, Xiaoting Qiao","doi":"10.1080/15384047.2024.2425127","DOIUrl":"10.1080/15384047.2024.2425127","url":null,"abstract":"<p><p>Cyclophilin A (CypA), a member of the immunophilin family, stands out as the most prevalent among the cyclophilins found in humans. Beyond serving as the intracellular receptor for the immunosuppressive drug cyclosporine A (CsA), CypA exerts critical functions within the cell via its <i>peptidyl-prolyl cis-trans isomerase</i> (<i>PPIase</i>) activity, which is crucial for processes, such as protein folding, trafficking, assembly, modulation of immune responses, and cell signaling. Increasing evidence indicates that CypA is up-regulated in a variety of human cancers and it may be a novel potential therapeutic target for cancer treatment. Therefore, gaining a thorough understanding of CypA's contribution to cancer could yield fresh perspectives and inform the development of innovative therapeutic approaches. This review delves into the multifaceted roles of CypA in cancer biology and explores the therapeutic potential of targeting CypA.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2425127"},"PeriodicalIF":5.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα.","authors":"Zhenyuan Qian, Wenfa Lin, Xufan Cai, Jianzhang Wu, Kun Ke, Zaiyuan Ye, Fang Wu","doi":"10.1080/15384047.2023.2299288","DOIUrl":"10.1080/15384047.2023.2299288","url":null,"abstract":"<p><p>Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2299288"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic silencing <i>ZSCAN23</i> promotes pancreatic cancer growth by activating Wnt signaling.","authors":"Qian Du, Meiying Zhang, Aiai Gao, Tao He, Mingzhou Guo","doi":"10.1080/15384047.2024.2302924","DOIUrl":"10.1080/15384047.2024.2302924","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the most malignant tumor. Zinc finger and SCAN domain-containing protein 23 (<i>ZSCAN23</i>) is a new member of the SCAN domain family. The expression regulation and biological function remain to be elucidated. In this study, we explored the epigenetic regulation and the function of <i>ZSCAN23</i> in PDAC. <i>ZSCAN23</i> was methylated in 60.21% (171/284) of PDAC and its expression was regulated by promoter region methylation. The expression of <i>ZSCAN23</i> inhibited cell proliferation, colony formation, migration, invasion, and induced apoptosis and G1/S phase arrest. <i>ZSCAN23</i> suppressed Panc10.05 cell xenograft growth in mice. Mechanistically, <i>ZSCAN23</i> inhibited Wnt signaling by interacting with myosin heavy chain 9 (MYH9) in pancreatic cancer cells. <i>ZSCAN23</i> is frequently methylated in PDAC and may serve as a detective marker. <i>ZSCAN23</i> suppresses PDAC cell growth both <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2302924"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells.","authors":"Yu-Yan Wang, Lian-Hua Ye, An-Qi Zhao, Wei-Ran Gao, Ning Dai, Yu Yin, Xin Zhang","doi":"10.1080/15384047.2024.2306674","DOIUrl":"10.1080/15384047.2024.2306674","url":null,"abstract":"<p><p>DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured <i>in vitro</i>. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2306674"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}