Cell Cycle最新文献

{"title":"Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A.","authors":"Michał Wójcik, Nikola Zmarzły, Alicja Derkacz, Tomasz Kulpok-Bagiński, Natasza Blek, Beniamin Oskar Grabarek","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and microRNA (miRNA) molecules potentially regulating their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes exposed to bacterial lipopolysaccharide A (LPS) and cyclosporine A (CsA). HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The molecular analysis consists of microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. The statistical analysis of the obtained results was performed using Transcriptome Analysis Console and STATISTICA 13.5 PL with the statistical significance threshold of <i>p</i> < 0.05. Changes in the expression profile of six mRNAs: dual-specificity phosphatase 1 (<i>DUSP1)</i>, dual-specificity phosphatase 4 (<i>DUSP4)</i>, mitogen-activated protein kinase kinase 2 (<i>MAP2K2)</i>, mitogen-activated protein kinase kinase 7 (<i>MAP2K7)</i>, mitogen-activated protein kinase kinase kinase 2 (<i>MAP3K2)</i> and mitogen-activated protein kinase 9 (<i>MAPK9)</i> in cell culture exposed to LPS or LPS and the drug compared to the control. We observed that under the LPS and cyclosporine treatment, the expression o/ miR-34a, miR-1275, miR-3188, and miR-382 changed significantly (<i>p</i> < 0.05). We demonstrated a potential relationship between <i>DUSP1</i> and miR-34a; <i>DUSP4</i> and miR-34a, miR-382, and miR-3188; <i>MAPK9</i> and miR-1275, <i>MAP2K7</i> and mir-200-5p; <i>MAP3K2</i> and mir-200-5p, which may be the subject of further research in the context of psoriasis.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/β-catenin pathway.","authors":"Ping Ma, Huajiao Yu, Mingda Zhu, Li Liu, Luyao Cheng, Zhengxue Han, Wulong Jin","doi":"10.1080/15384101.2024.2348918","DOIUrl":"10.1080/15384101.2024.2348918","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a poor prognosis, yet the underlying mechanism needs further exploration. Non-SMC condensin I complex subunit D2 (NCAPD2) is a widely expressed protein in OSCC, but its role in tumor development is unclear. This study aimed to explore NCAPD2 expression and its biological function in OSCC. NCAPD2 expression in OSCC cell lines and tissue specimens was analyzed using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cancer cell growth was evaluated using cell proliferation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and colony formation assays. Cell migration was evaluated using wound healing and Transwell assays. Apoptosis was detected using flow cytometry. The influence of NCAPD2 on tumor growth <i>in vivo</i> was evaluated in a mouse xenograft model. NCAPD2 expression was significantly higher in OSCC than that in normal oral tissue. <i>In vitro</i>, the knockdown of NCAPD2 inhibited OSCC cell proliferation and promoted apoptosis. NCAPD2 depletion also significantly inhibited the migration of OSCC cells. Moreover, NCAPD2 overexpression induced inverse effects on OSCC cell phenotypes. <i>In vivo</i>, we demonstrated that downregulating NCAPD2 could inhibit the tumorigenicity of OSCC cells. Mechanically, OSCC regulation by NCAPD2 involved the Wnt/β-catenin signaling pathway. These results suggest <i>NCAPD2</i> as a novel oncogene with an important role in OSCC development and a candidate therapeutic target for OSCC.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"588-601"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UHRF2 accumulates in early G₁-phase after serum stimulation or mitotic exit to extend G₁ and total cell cycle length.","authors":"Xiaohong Wang, Huarui Lu, Grace Sprangers, Timothy C Hallstrom","doi":"10.1080/15384101.2024.2353553","DOIUrl":"10.1080/15384101.2024.2353553","url":null,"abstract":"<p><p>Ubiquitin like with PHD and ring finger domains 2 (UHRF2) regulates the cell cycle and epigenetics as a multi-domain protein sharing homology with UHRF1. UHRF1 functions with DNMT1 to coordinate daughter strand methylation during DNA replication, but UHRF2 can't perform this function, and its roles during cell cycle progression are not well defined. UHRF2 role as an oncogene vs. tumor suppressor differs in distinct cell types. UHRF2 interacts with E2F1 to control Cyclin E1 (<i>CCNE1</i>) transcription. UHRF2 also functions in a reciprocal loop with Cyclin E/CDK2 during G₁, first as a direct target of CDK2 phosphorylation, but also as an E3-ligase with direct activity toward both Cyclin E and Cyclin D. In this study, we demonstrate that UHRF2 is expressed in early G₁ following either serum stimulation out of quiescence or in cells transiting directly out of M-phase, where UHRF2 protein is lost. Further, UHRF2 depletion in G2/M is reversed with a CDK1 specific inhibitor. UHRF2 controls expression levels of cyclins and CDK inhibitors and controls its own transcription in a negative-feedback loop. Deletion of <i>UHRF2</i> using CRISPR/Cas9 caused a delay in passage through each cell cycle phase. UHRF2 loss culminated in elevated levels of cyclins but also the CDK inhibitor p27^KIP1, which regulates G₁ passage, to reduce retinoblastoma phosphorylation and increase the amount of time required to reach G₁/S passage. Our data indicate that UHRF2 is a central regulator of cell-cycle pacing through its complex regulation of cell cycle gene expression and protein stability.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"613-627"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudogene OCT4-pg5 upregulates OCT4B expression to promote bladder cancer progression by competing with miR-145-5p.","authors":"Wuer Zhou, Yue Yang, Wei Wang, Chenglin Yang, Zhi Cao, Xiaoyu Lin, Huifen Zhang, Yuansong Xiao, Xiaoming Zhang","doi":"10.1080/15384101.2024.2353554","DOIUrl":"10.1080/15384101.2024.2353554","url":null,"abstract":"<p><p>Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3' untranslated region (3'UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/β-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"645-661"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surfeit locus protein 4 modulates endoplasmic reticulum function and maintains oocyte quality.","authors":"Yuanyuan Li, Li-Quan Zhou, Ying Yin","doi":"10.1080/15384101.2024.2360287","DOIUrl":"10.1080/15384101.2024.2360287","url":null,"abstract":"<p><p>Surfeit locus protein 4 is a cargo receptor mediating cargo transport from the endoplasmic reticulum lumen to the Golgi apparatus. Loss of <i>Surf4</i> gene led to embryonic lethality in mice. However, the role of <i>Surf4</i> during oocyte development remains unknown. In this study, we generated the mouse model with oocyte-specific knockout of <i>Surf4</i> gene. We found that adult mice with deletion of <i>Surf4</i> showed normal folliculogenesis, ovulation and fertility. However, loss of <i>Surf4</i> slightly impaired oocyte quality, thus led to partial oocyte meiotic arrest and reduced ratio of blastocyst formation. Consistent with this, the distribution of endoplasmic reticulum was disturbed in <i>Surf4</i>-deficient oocytes in mice. These results demonstrated that although <i>Surf4</i> is dispensable for female mouse fertility, <i>Surf4</i> modulates endoplasmic reticulum arrangement and participates in regulation of developmental competence of oocytes.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"703-712"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of endogenous hydrogen sulfide production reduces activation of hepatic stellate cells via the induction of cellular senescence.","authors":"Turtushikh Damba, Mengfan Zhang, Sandra A Serna Salas, Zongmei Wu, Harry van Goor, Aaron Fierro Arenas, Martin Humberto Muñoz-Ortega, Javier Ventura-Juárez, Manon Buist-Homan, Han Moshage","doi":"10.1080/15384101.2024.2345477","DOIUrl":"10.1080/15384101.2024.2345477","url":null,"abstract":"<p><p>In chronic liver injury, quiescent hepatic stellate cells (HSCs) transdifferentiate into activated myofibroblast-like cells and produce large amounts of extracellular matrix components, e.g. collagen type 1. Cellular senescence is characterized by irreversible cell-cycle arrest, arrested cell proliferation and the acquisition of the senescence-associated secretory phenotype (SASP) and reversal of HSCs activation. Previous studies reported that H₂S prevents induction of senescence via its antioxidant activity. We hypothesized that inhibition of endogenous H₂S production induces cellular senescence and reduces activation of HSCs. Rat HSCs were isolated and culture-activated for 7 days. After activation, HSCs treated with H₂S slow-releasing donor GYY4137 and/or DL-propargylglycine (DL-PAG), an inhibitor of the H2S-producing enzyme cystathionine γ-lyase (CTH), as well as the PI3K inhibitor LY294002. In our result, CTH expression was significantly increased in fully activated HSCs compared to quiescent HSCs and was also observed in activated stellate cells in a <i>in vivo</i> model of cirrhosis. Inhibition of CTH reduced proliferation and expression of fibrotic markers <i>Col1a1</i> and <i>Acta2</i> in HSCs. Concomitantly, DL-PAG increased the cell-cycle arrest markers <i>Cdkn1a (p21)</i>, <i>p53</i> and the SASP marker <i>Il6</i>. Additionally, the number of β-galactosidase positive senescent HSCs was increased. GYY4137 partially restored the proliferation of senescent HSCs and attenuated the DL-PAG-induced senescent phenotype. Inhibition of PI3K partially reversed the senescence phenotype of HSCs induced by DL-PAG. Inhibition of endogenous H₂S production reduces HSCs activation via induction of cellular senescence in a PI3K-Akt dependent manner. Our results show that cell-specific inhibition of H₂S could be a novel target for anti-fibrotic therapy via induced cell senescence.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"629-644"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy-induced senescence is finally escapable, what is next?","authors":"Tareq Saleh","doi":"10.1080/15384101.2024.2364579","DOIUrl":"10.1080/15384101.2024.2364579","url":null,"abstract":"<p><p>Several breakthrough articles have recently confirmed the ability of tumor cells to escape the stable cell cycle arrest imposed by Therapy-Induced Senescence (TIS). Subsequently, accepting the hypothesis that TIS is escapable should encourage serious reassessments of the fundamental roles of senescence in cancer treatment. The potential for escape from TIS undermines the well-established tumor suppressor function of senescence, proposes it as a mechanism of tumor dormancy leading to disease recurrence and invites for further investigation of its unfavorable contribution to cancer therapy outcomes. Moreover, escaping TIS strongly indicates that the elimination of senescent tumor cells, primarily through pharmacological means, is a suitable approach for increasing the efficacy of cancer treatment, one that still requires further exploration. This commentary provides an overview of the recent evidence that unequivocally demonstrated the ability of therapy-induced senescent tumor cells in overcoming the terminal growth arrest fate and provides future perspectives on the roles of TIS in tumor biology.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"713-721"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained activation of NF-κB through constitutively active IKKβ leads to senescence bypass in murine dermal fibroblasts.","authors":"Masayuki Harada, Kanae Su-Harada, Takeshi Kimura, Koh Ono, Noboru Ashida","doi":"10.1080/15384101.2024.2325802","DOIUrl":"10.1080/15384101.2024.2325802","url":null,"abstract":"<p><p>Although the transcription factor nuclear factor κB (NF-κB) plays a central role in the regulation of senescence-associated secretory phenotype (SASP) acquisition, our understanding of the involvement of NF-κB in the induction of cellular senescence is limited. Here, we show that activation of the canonical NF-κB pathway suppresses senescence in murine dermal fibroblasts. IκB kinase β (IKKβ)-depleted dermal fibroblasts showed ineffective NF-κB activation and underwent senescence more rapidly than control cells when cultured under 20% oxygen conditions, as indicated by senescence-associated β-galactosidase (SA-β-gal) staining and <i>p16^INK4a</i> mRNA levels. Conversely, the expression of <u>c</u>onstitutively <u>a</u>ctive IKKβ (IKKβ-CA) was sufficient to drive senescence bypass. Notably, the expression of a degradation-resistant form of inhibitor of κB (IκB), which inhibits NF-κB nuclear translocation, abolished senescence bypass, suggesting that the inhibitory effect of IKKβ-CA on senescence is largely mediated by NF-κB. We also found that IKKβ-CA expression suppressed the derepression of <i>INK4/Arf</i> genes and counteracted the senescence-associated loss of <i>Ezh2</i>, a catalytic subunit of the Polycomb repressive complex 2 (PRC2). Moreover, pharmacological inhibition of Ezh2 abolished IKKβ-CA-induced senescence bypass. We propose that NF-κB plays a suppressive role in the induction of stress-induced senescence through sustaining <i>Ezh2</i> expression.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"308-327"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab.","authors":"Michał Wójcik, Aleksandra Plata-Babula, Amelia Głowaczewska, Tomasz Sirek, Aneta Orczyk, Mariola Małecka, Beniamin Oskar Grabarek","doi":"10.1080/15384101.2024.2335051","DOIUrl":"10.1080/15384101.2024.2335051","url":null,"abstract":"<p><p>Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAPKs and microRNA (miRNA) molecules that potentially regulate their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes when exposed to bacterial lipopolysaccharide A (LPS) and adalimumab. HaCaT cells underwent treatment with 1 µg/mL LPS for 8 hours, followed by treatment with 8 µg/mL adalimumab for 2, 8, or 24 hours. Untreated cells served as controls. The molecular analysis involved microarray, quantitative real-time polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA) analyses. Changes in the expression profile of seven mRNAs: dual specificity phosphatase 1 (<i>DUSP1)</i>, dual specificity phosphatase 3 (<i>DUSP3)</i>, dual specificity phosphatase 4 (<i>DUSP4)</i>, mitogen-activated protein kinase 9 (<i>MAPK9)</i>, mitogen-activated protein kinase kinase kinase 2 (<i>MAP3K2)</i>, mitogen-activated protein kinase kinase 2 (<i>MAP2K2), and</i> MAP kinase-activated protein kinase 2 <i>(MAPKAPK2</i>, also known as <i>MK2)</i> in cell culture exposed to LPS or LPS and the drug compared to the control. It was noted that miR-34a may potentially regulate the activity of <i>DUSP1</i>, <i>DUSP3</i>, and <i>DUSP4</i>, while miR-1275 is implicated in regulating <i>MAPK9</i> expression. Additionally, miR-382 and miR-3188 are potential regulators of <i>DUSP4</i> levels, and miR-200-5p is involved in regulating <i>MAPKAPK2</i> and <i>MAP3K2</i> levels. Thus, the analysis showed that these mRNA molecules and the proteins and miRNAs they encode appear to be useful molecular markers for monitoring the efficacy of adalimumab therapy.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"385-404"},"PeriodicalIF":4.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of hCINAP sensitizes colorectal cancer cells to ionizing radiation.","authors":"Meizhu Shen, Yong Zhang, Fang Wu, Meizhen Shen, Sen Zhang, Yun Guo, Jialiang Gan, Rensheng Wang","doi":"10.1080/15384101.2024.2309015","DOIUrl":"10.1080/15384101.2024.2309015","url":null,"abstract":"<p><p>Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoroughly explored. This study aimed to shed light on the role of human coilin interacting nuclear ATPase protein (hCINAP) in radiation-resistant HT-29 and SW480 CRC cells (HT-29-IR and SW480-IR) and investigate its potential implications. Firstly, radiation-resistant CRC cell lines were established by subjecting HT-29 and SW480 cells to sequential radiation exposure. Subsequent analysis revealed a notable increase in hCINAP expression in radiation-resistant CRC cells. To elucidate the functional role of hCINAP in radio-resistance, knockdown experiments were conducted. Remarkably, knockdown of hCINAP resulted in an elevation of reactive oxygen species (ROS) generation upon radiation treatment and subsequent activation of apoptosis mediated by mitochondria. These observations indicate that hCINAP depletion enhances the radiosensitivity of CRC cells. Conversely, when hCINAP was overexpressed, it was found to enhance the radio-resistance of CRC cells. This suggests that elevated hCINAP expression contributes to the development of radio-resistance. Further investigation revealed an interaction between hCINAP and ATPase family AAA domain containing 3A (ATAD3A). Importantly, ATAD3A was identified as an essential factor in hCINAP-mediated radio-resistance. These findings establish the involvement of hCINAP and its interaction with ATAD3A in the regulation of radio-resistance in CRC cells. Overall, the results of this study demonstrate that upregulating hCINAP expression may improve the survival of radiation-exposed CRC cells. Understanding the intricate molecular mechanisms underlying hCINAP function holds promise for potential strategies in targeted radiation therapy for CRC. These findings emphasize the importance of further research to gain a comprehensive understanding of hCINAP's precise molecular mechanisms and explore its potential as a therapeutic target in overcoming radio-resistance in CRC. By unraveling the complexities of hCINAP and its interactions, novel therapeutic approaches may be developed to enhance the efficacy of radiation therapy and improve outcomes for CRC patients.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"233-247"},"PeriodicalIF":3.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}