细胞周期蛋白O通过调控糖酵解促进宫颈癌细胞增殖和转移

刘静波; 张媛; 刘梦君; 刘静; 刘红丽; 张競

doi:10.12259/j.issn.2095-610X.S20250710

细胞周期蛋白O通过调控糖酵解促进宫颈癌细胞增殖和转移

doi: 10.12259/j.issn.2095-610X.S20250710

蚌埠医科大学第一附属医院肿瘤妇科，安徽蚌埠　233000

基金项目: 安徽省高等学校科学研究自然科学重点项目（2024AH051293）；蚌埠医科大学科技项目自然科学重点项目（2023byzd066）

详细信息

作者简介:
刘静波（1987～），女，安徽蚌埠人，医学硕士，副主任医师，主要从事妇科常见恶性肿瘤的临床及基础研究工作

通讯作者:
张競，E-mail：zhangjing1179@163.com

中图分类号: R737.33
计量
- 文章访问数: 331
- HTML全文浏览量: 138
- PDF下载量: 12
- 被引次数: 0
出版历程
- 收稿日期: 2025-03-18
- 刊出日期: 2025-07-21

Cyclin O Promotes the Proliferation and Metastasis of Cervical Cancer Cells by Regulating Glycolysis

Department of Oncology and Gynecology，The First Affiliated Hospital of Bengbu Medical University，Bengbu Anhui 233000，China

摘要

摘要: 目的探讨细胞周期蛋白O（cyclin O，CCNO）在宫颈癌中的表达及影响宫颈癌进展的分子机制。方法收集2018年1月至2023年12月期间蚌埠医科大学第一附属医院肿瘤妇科60例宫颈癌患者病理切片，免疫组化检测CCNO在宫颈癌中的表达。通过转染技术将实验分为Vector组、CCNO组、siNC和siCCNO组。通过CCK-8实验及克隆形成实验评估CCNO影响细胞增殖水平的能力。利用Transwell小室实验及划痕实验评估CCNO影响细胞侵袭及迁移能力。利用糖酵解实验及蛋白印迹实验评估CCNO对宫颈癌细胞糖酵解的影响。结果临床样本免疫组化及WB结果显示，CCNO在宫颈癌中高表达（P < 0.001）。实验发现过表达CCNO促进宫颈癌细胞增殖、侵袭、迁移及糖酵解的发生（P < 0.05），反之则抑制宫颈癌细胞增殖、侵袭、迁移及糖酵解（P < 0.05）。生信分析及WB实验结果显示，过表达CCNO可能通过激活PI3K/AKT信号通路调节宫颈癌的发生（P < 0.05）。结论细胞周期蛋白O可能通过调控糖酵解促进宫颈癌细胞增殖和转移。
- CCNO /
- 糖酵解代谢 /
- 宫颈癌 /
- PI3K/AKT信号通路
Abstract: Objective To investigate the expression of Cyclin O （CCNO） in cervical cancer and its molecular mechanism in the progression of cervical cancer. Methods The pathological sections of 60 patients with cervical cancer in the Department of Oncology and Gynecology of the First Affiliated Hospital of Bengbu Medical University from January 2018 to December 2023 were collected, and the expression of CCNO in cervical cancer was detected by immunohistochemistry. The cells were divided into Vector group, CCNO group, siNC group and siCCNO group by transfection technology. CCK-8 assay and colony formation assay were used to evaluate the ability of CCNO to affect cell proliferation. Transwell assay and wound healing assay were used to evaluate the effect of CCNO on cell invasion and migration. Glycolysis assay and Western blot assay were used to evaluate the effect and mechanism of CCNO on glycolysis of cervical cancer cells. Results The results of immunohistochemistry and WB showed that CCNO was highly expressed in cervical cancer （P < 0.001）. Overexpression of CCNO promoted the proliferation, invasion, migration and glycolysis of cervical cancer cells （P < 0.05）, whereas the opposite effect inhibited the proliferation, invasion, migration and glycolysis of cervical cancer cells （P < 0.05）. Bioinformatics analysis and WB results showed that CCNO overexpression may regulate the occurrence of cervical cancer by activating the PI3K/AKT signaling pathway （P < 0.05）. Conclusion Cyclin O may promote the proliferation and metastasis of cervical cancer cells by regulating glycolysis.
- CCNO /
- Glycolysis and metabolism /
- Cervical cancer /
- PI3K/AKT signaling pathway

HTML全文

图 1 CCNO在宫颈癌中表达情况

A：TCGA数据库中CCNO在宫颈癌中的表达情况；B：ROC曲线；C：免疫组化检测宫颈癌患者样本中CCNO的表达（×100、×400）；D：Western blot检测宫颈癌患者样本中CCNO的表达；^*P < 0.05。

Figure 1. Expression of CCNO in cervical cancer

下载: 全尺寸图片幻灯片

图 2 CCNO在宫颈癌细胞中表达情况及转染效率检测（$\bar x \pm s $，n = 3）

A：RT-PCR检测CCNO宫颈癌细胞系；B：WB检测CCNO宫颈癌细胞系；C～D：RT-PCR和WB检测CCNO的转染效率；^*P < 0.05。

Figure 2. CCNO expression and transfection efficiency in cervical cancer cells were detected （$\bar x \pm s $，n = 3）

下载: 全尺寸图片幻灯片

图 3 CCNO影响宫颈癌细胞的增殖情况（$\bar x \pm s $，n = 3）

A：CCK-8实验; B：克隆形成实验；^*P < 0.05。

Figure 3. Effects of CCNO on cervical cancer cell proliferation （$\bar x \pm s $，n = 3）

下载: 全尺寸图片幻灯片

图 4 CCNO影响宫颈癌细胞的侵袭、迁移（×40）

A：宫颈癌细胞小室实验；B：宫颈癌细胞划痕实验；^*P < 0.05。

Figure 4. Effects of CCNO on cervical cancer cell invasion and migration（×40）

下载: 全尺寸图片幻灯片

图 5 CCNO调控糖酵

A：KEGG分析中糖酵解途径富集；B：KEGG富集糖酵解通路；C：WB检测糖酵解相关酶的蛋白表达；^*P < 0.05。

Figure 5. Regulation of glycolysis by CCNO

下载: 全尺寸图片幻灯片

图 6 CCNO通过PI3K/AKT信号通路调控宫颈癌

A：在SIHa中发现敲减CCNO影响的差异表达基因富集的KEGG通路；B：WB验证信号通路蛋白表达；^*P < 0.05。

Figure 6. Regulation of cervical cancer by CCNO via the PI3K/AKT signaling pathway

下载: 全尺寸图片幻灯片

表 1 引物序列

Table 1. Primer sequence

基因名称	上游	下游
CCNO	5′- TCCAGTCAGGAGGCTGAGTT-3′	5′-CAAAAGGCATTCCAGCATTT-3′
GAPDH	5′-GCACCGTCAAGGCTGAGAAC-3′	5′-TGGTGAAGACGCCAGTGGA-3′

下载: 导出CSV

表 2 CCNO在宫颈癌组织及癌旁组织中的表达水平[n （%）]

Table 2. Expression levels of CCNO in Cervical cancer tissues and adjacent tissues[n （%）]

CCNO表达	癌组织（n=60）	癌旁组织（n=60）	χ²	P
阳性	48（80.0）	8（13.3）	53.571	< 0.001^*
阴性	12（20.0）	52（86.7）
^*P < 0.05。

下载: 导出CSV

表 3 宫颈癌患者CCNO表达与临床资料的关系（n）

Table 3. Relationship between CCNO expression and clinical data in patients with cervical cancer （n）

特征	n	CCNO 表达		χ²	p
特征	n	高	低	χ²	p
年龄（岁）				0.268	0.605
< 50	32	17	15
≥50	28	13	15
HPV感染				1.086	0.297
阴性	34	19	15
阳性	26	11	15
肿瘤大小（cm）				6.787	0.009^*
< 3	26	8	18
≥3	34	22	12
FIGO分期				4.344	0.037^*
Ⅰ	26	9	17
Ⅱ～Ⅲ	34	21	13
淋巴结转移				8.076	0.004^*
有	31	21	10
无	29	9	20
组织类型				3.300	0.069
鳞癌	27	17	10
腺癌	33	13	20
^*P < 0.05。

下载: 导出CSV

参考文献(20)

[1]	Bray F,Laversanne M,Sung H,et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2024,74(3):229-263. doi: 10.3322/caac.21834
[2]	Siegel R L,Miller K D,Wagle N S,et al. Cancer statistics,2023[J]. CA:A Cancer J Clinicians,2023,73(1):17-48. doi: 10.3322/caac.21763
[3]	Xia C,Dong X,Li H,et al. Cancer statistics in China and United States,2022: Profiles,trends,and determinants[J]. Chin Med J (Engl),2022,135(5):584-590. doi: 10.1097/CM9.0000000000002108
[4]	Chen C Y, Chen W C, Mohamed M G,et al. Highly thermally stable,reversible,and flexible main chain type benzoxazine hybrid Incorporating both polydimethylsiloxane and double-decker shaped polyhedral silsesquioxane units through diels-alder reaction[J]. Macromol Rapid Commun,2023,44(10):e2200910. doi: 10.1002/marc.202200910
[5]	Oaknin A,Moore K,Meyer T,et al. Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): A phase 1-2,open-label,multicohort trial[J]. Lancet Oncol,2024,25(5):588-602. doi: 10.1016/S1470-2045(24)00088-3
[6]	Jiang J,Yu W,Fang T,et al. Cyclin O promotes lung cancer progression and cetuximab resistance via cell cycle regulation and CDK13 interaction[J]. J Thorac Dis,2023,15(4):2167-2183. doi: 10.21037/jtd-23-437
[7]	Li L,Cao Y,Zhou H,et al. Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis[J]. Onco Targets Ther,2018,11:7471-7481. doi: 10.2147/OTT.S176252
[8]	Amirav I,Wallmeier J,Loges N T,et al. Systematic analysis of CCNO variants in a defined population: Implications for clinical phenotype and differential diagnosis[J]. Hum Mutat,2016,37(4):396-405. doi: 10.1002/humu.22957
[9]	Roig M B,Roset R,Ortet L,et al. Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells[J]. Cell Death Differ,2009,16(2):230-243. doi: 10.1038/cdd.2008.145
[10]	Ma J Y,Ou-Yang Y C,Luo Y B,et al. Cyclin O regulates germinal vesicle breakdown in mouse oocytes[J]. Biol Reprod,2013,88(5):110.
[11]	Wallmeier J,Al-Mutairi D A,Chen C T,et al. Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile Cilia[J]. Nat Genet,2014,46(6):646-651. doi: 10.1038/ng.2961
[12]	Li L, Cao Y, Zhou H, et al. Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis[J]. Onco Targets Ther,2018,11:7471-7481.
[13]	仲娣,刘子曈,李鹏,等. 宫颈癌组织中YTHDF1的表达及其临床意义[J]. 徐州医科大学学报,2024,44(8):553-558. doi: 10.12467/j.issn.2096-3882.20240315
[14]	Song Z,Wei Z,Wang Q,et al. The role of DOT1L in the proliferation and prognosis of gastric cancer[J]. Biosci Rep,2020,40(1):BSR20193515. doi: 10.1042/BSR20193515
[15]	Yao S,Zhao L,Chen S,et al. Cervical cancer immune infiltration microenvironment identification,construction of immune scores,assisting patient prognosis and immunotherapy[J]. Front Immunol,2023,14:1135657. doi: 10.3389/fimmu.2023.1135657
[16]	Kamamoto S, Murayama A, Hamaki T, et al. HPV vaccination and cervical cancer screening.[J]. Lancet.,2022,399(10339):1939-1940.
[17]	Falcaro M,Soldan K,Ndlela B,et al. Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: Population based observational study[J]. BMJ,2024,385:e077341.
[18]	Rahangdale L,Mungo C,O'Connor S,et al. Human papillomavirus vaccination and cervical cancer risk[J]. BMJ,2022,379:e070115.
[19]	Wang J,Chen S. RACK1 promotes miR-302b/c/d-3p expression and inhibits CCNO expression to induce cell apoptosis in cervical squamous cell carcinoma[J]. Cancer Cell Int,2020,20:385. doi: 10.1186/s12935-020-01435-0
[20]	Fujimura A,Michiue H,Cheng Y,et al. Cyclin G2 promotes hypoxia-driven local invasion of glioblastoma by orchestrating cytoskeletal dynamics[J]. Neoplasia,2013,15(11):1272-1281. doi: 10.1593/neo.131440

相关文章(20)

[1]	唐晓玲, 谢帮芳, 黄海龙. 外泌体miR-210-3p通过靶向FBXO31促进宫颈癌的化疗耐药和干细胞特性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20250707
[2]	严怡然, 沈成万, 尚香玉, 冯婵, 李金秋, 阿仙姑·哈斯木. 高良姜素通过影响Hippo/YAP通路抑制宫颈癌Hela细胞迁移和侵袭, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20250105
[3]	孟丽燕, 王超群, 陈星慧, 何军晶, 牛雅茹, 马丽莎. 早期宫颈癌术后HPV持续感染的危险因素分析, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240422
[4]	肖金宝, 赵骏达, 马俊旗. 下调HPV16 E6/E7表达宫颈癌细胞Siha上清液代谢组学, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240104
[5]	秦祥川, 李金秋, 黄晓婧, 忽吐比丁·库尔班, 阿仙姑·哈斯木. HPV E6通过Rap1信号通路影响宫颈癌细胞增殖、侵袭及迁移的研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240902
[6]	郭妮, 张承, 洪超, 刘伟鹏, 姚宇峰, 严志凌. KRAS基因3′UTR多态性与云南汉族人群宫颈癌及宫颈上皮内瘤变的相关性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240203
[7]	海燕, 美力班·吐尔逊, 阿仙姑·哈斯木. Pin1通过调控脂质代谢关键酶影响宫颈癌细胞的增殖及凋亡, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230107
[8]	李婷, 郭维华. 糖酵解重编程在口腔鳞状细胞癌中的研究进展, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230611
[9]	谢芹, 赵春阳, 张葆溯, 赵洪波. 硫利达嗪抗宫颈癌的潜在作用机制, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220317
[10]	刘洋, 廖婧, 卢又汇, 孙春意, 孟昱时. miR-21负向调控宫颈癌HeLa细胞株中hTERT的表达, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210307
[11]	张娟, 张红芸. 宫颈管搔刮术在宫颈癌筛查中的价值, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210822
[12]	谭丁及, 尹洪莉, 朱锐, 张曦, 余鑫, 飞勇, 李昕, 段铭, 何亮, 杨宏英. 宫颈上皮内瘤变和宫颈癌患者的阴道微生态特点, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210821
[13]	郝立君, 徐丽秀, 李金秋, 马俊旗, 阿仙姑·哈斯木. 肽基脯氨酰同分异构酶（Pin1）对子宫颈癌细胞脂质代谢的作用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210111
[14]	卿清, 刘洋, 周红林. 宫颈癌筛查策略的研究进展, 昆明医科大学学报.
[15]	周栩茹, 王熙, 田洁, 谢玲玲, 许宏宇, 李晓兰. 黏附斑激酶在宫颈癌组织中表达及意义, 昆明医科大学学报.
[16]	王雅楠, 李治纲, 张超, 李树德, 李涛, 彭建志. 同型半胱氨酸通过促进脂肪组织TRB3表达抑制PI3K/Akt信号通路, 昆明医科大学学报.
[17]	何红芬. 宫颈锥切术治疗IaⅠ期宫颈癌患者术后病灶残余状况及其危险因素, 昆明医科大学学报.
[18]	魏洁. Twist在中晚期宫颈癌组织中的表达及临床意义研究, 昆明医科大学学报.
[19]	刘慧瑾. 宫颈癌组织Vimentin的表达与淋巴转移宫旁浸润的关系研究, 昆明医科大学学报.
[20]	黄雅. Brn-3a、PPAR-γ在宫颈癌及癌前病变中的表达, 昆明医科大学学报.