CBX2 Promotes Proliferation，Invasion，and Glycolysis of Cervical Cancer Cells by Regulating the JAK2/STAT3 Signaling Pathway
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摘要:
目的 探讨色盒同源物2（chromoboxhomolog 2，CBX2）在宫颈癌中的表达情况及作用机制。 方法 收集蚌埠医科大学第二附属医院妇产科2022年1月至2024年12月期间的60例宫颈癌患者临床标本组织切片，使用免疫组化、RT-PCR及蛋白印迹实验检测CBX2在宫颈癌中的表达情况。利用转染分子技术将实验分为si-NC组、si-CBX2组、oe-NC和oe-CBX2组。通过克隆形成实验与蛋白印迹实验，验证CBX2对宫颈癌细胞增殖水平的影响能力。借助Transwell小室实验和划痕实验，检测CBX2对细胞侵袭及迁移能力的作用。最后利用蛋白印迹实验检测CBX2对宫颈癌细胞糖酵解的影响及机制研究。 结果 临床样本的免疫组化、RT-PCR以及蛋白印迹实验结果表明，CBX2在宫颈癌里呈现高表达（P < 0.05）。实验表明敲减CBX2能够抑制宫颈癌细胞的增殖、转移与糖酵解过程（P < 0.05）。相反，CBX2过表达则会促进宫颈癌细胞的增殖、转移和糖酵解过程（P < 0.05）。蛋白印迹实验结果提示，CBX2过表达或许可通过激活JAK2/STAT3信号通路来调控宫颈癌细胞生物学行为（P < 0.05）。 结论 CBX2通过调控JAK2 /STAT3信号通路促进宫颈癌细胞增殖、转移及糖酵解。 -
关键词:
- 色盒同源物2 /
- 糖酵解代谢 /
- 宫颈癌 /
- JAK2 /STAT3信号通路
Abstract:Objective To investigate the expression pattern and mechanism of Chromobox homolog 2 （CBX2） in cervical cancer. Methods Clinical tissue specimens from 60 patients with cervical cancer were collected from the Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Bengbu Medical College between January 2022 and December 2024. CBX2 expression in cervical cancer was detected using immunohistochemistry, RT-PCR, and Western blotting. Through transfection techniques, cells were divided into four experimental groups: si-NC （negative control）, si-CBX2, oe-NC , and oe-CBX2 . Colony formation assays and Western blotting were used to assess the effect of CBX2 on cervical cancer cell proliferation. Transwell chamber assays and wound healing assays were conducted to evaluate the effect of CBX2 on cell invasion and migration. Finally, Western blotting was employed to assess the impact and potential mechanism of CBX2 on glycolysis in cervical cancer cells. Results Immunohistochemistry, RT-PCR, and Western blot analyses of clinical samples revealed that CBX2 was highly expressed in cervical cancer tissues （P < 0.05）. In vitro experiments demonstrated that knockdown of CBX2 significantly inhibited the proliferation, metastasis, and glycolysis of cervical cancer cells （P < 0.05）. Conversely, overexpression of CBX2 promoted these processes （P < 0.05）. Furthermore, Western blot results suggested that CBX2 overexpression might regulate the biological behavior of cervical cancer cells by activating the JAK2/STAT3 signaling pathway （P < 0.05）. Conclusion CBX2 promotes proliferation, metastasis, and glycolysis in cervical cancer cells by regulating the JAK2/STAT3 signaling pathway. -
Key words:
- CBX2 /
- Glycolysis and metabolism /
- Cervical cancer /
- JAK2/STAT3 signaling pathway
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图 1 CBX2在宫颈癌中表达情况 （$ \bar x \pm s $，n = 3）
A：CBX2生信数据库宫颈癌中的表达情况；B：CBX2诊断ROC曲线；C～D：免疫组化检测宫颈癌患者样本中CBX2的表达情况（×100）；*P < 0.05，**P < 0.01。
Figure 1. Expression of CBX2 in cervical cancer （$ \bar x \pm s $，n = 3）
图 2 CBX2在宫颈癌细胞中表达情况及转染效率检测（$ \bar x \pm s $，n = 3）
A：RT-PCR检测CBX2宫颈癌细胞系表达情况；B：WB检测CBX2宫颈癌细胞系表达情况；C～D：RT-PCR和WB检测CBX2的转染效率；*P < 0.05。
Figure 2. CBX2 expression and transfection efficiency in cervical cancer cells （$ \bar x \pm s $，n = 3）
图 3 CBX2影响宫颈癌细胞增殖能力 （$ \bar x \pm s $，n = 3）
A：克隆形成实验; B：蛋白印迹实验检测增殖相关蛋白表达情况；*P < 0.05。
Figure 3. Effect of CBX2 on the proliferation of cervical cancer cells（$ \bar x \pm s $，n = 3）
图 4 CBX2影响宫颈癌细胞的侵袭、迁移（×40）（$ \bar x \pm s $，n = 3）
A：宫颈癌细胞小室实验；B：宫颈癌细胞Transwell小室实验；*P < 0.05。
Figure 4. Effect of CBX2 on cervical cancer cell invasion and migration（×40）（$ \bar x \pm s $，n = 3）
图 5 CBX2影响葡萄糖代谢蛋白表达水平（$ \bar x \pm s $，n = 3）
A：蛋白印迹实验检测代谢相关蛋白表达情况；B：葡萄糖消耗实验；*P < 0.05。
Figure 5. Effect of CBX2 on the expression levels of glucose metabolism-related proteins （$ \bar x \pm s $，n = 3）
图 6 CBX2影响JAK2 /STAT3信号通路情况（$ \overline{x} $±s ，n=3）
A：蛋白印迹实验检测JAK2 /STAT3信号相关蛋白表达情况；B：蛋白印迹实验检测实验结果；*P < 0.05。
Figure 6. Effect of CBX2 on the JAK2/STAT3 signaling pathway.
表 1 引物序列
Table 1. Primer sequences
基因名称 序列（5’→3’） CBX2 F：CTGTGTCAAGGGCAGTGCTA R：ATACGTGCTCGATGAGGCTG GAPDH F：CGGAGTCAACGGATTTGGTCGTAT R：AGCCTTCTCCATGGTGGTGAAGAC 
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表 2 宫颈癌患者CBX2表达与临床资料的关系[n（%）]
Table 2. Relationship betweenCBX2 expression and clinical characteristics in patients with cervical cancer[n（%）]
特征 n CBX2 表达 χ2 p 高 低 年龄（岁） <50 25 12（40.0） 13（43.3） 0.069 0.793 ≥50 35 18（60.0） 17（56.7） HPV感染 阴性 20 9（30） 11（36.7） 0.300 0.584 阳性 40 21（70.0） 19（63.3） 肿瘤大小（cm） <3 20 5（16.7） 15（50.0） 7.500 0.006* ≥3 40 25（83.3） 15（50.0） FIGO分期 Ⅰ 25 8（26.7） 17（56.7） 5.554 0.018* Ⅱ～Ⅲ 35 22（73.3） 13（43.3） 淋巴结转移 有 30 20（66.7） 10（33.3） 6.667 0.010* 无 30 10（33.3） 20（66.7） 组织类型 鳞癌 33 21（70.0） 12（40.0） 5.455 0.020* 腺癌 27 9（30.0） 18（60.0） *P < 0.05。
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