ALYREF调节BIRC5 mRNA的m5C修饰和稳定性，促进卵巢癌进展

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-05-29 DOI:10.1016/j.prp.2025.156055

Yongju Tian , Jianmeng Liu , Lei Sun , Xiaoguang Wang

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引用次数: 0

摘要

卵巢癌（OC）是妇科肿瘤中最危险的癌症，对全世界妇女的健康构成重大威胁。5-甲基胞嘧啶（5-methylcytosine, m5C）在调节肿瘤发生发展中起着重要作用。RNA甲基转移酶Aly/REF输出因子（ALYREF）是m5c修饰的RNA读取蛋白之一。尽管有报道称ALREF在多种癌症中发挥促进作用，但ALYREF在OC中的作用机制尚不清楚。方法应用生物信息学和western blot技术分析ALYREF在OC组织和细胞中的表达水平。采用CCK8、菌落形成、EdU、流式细胞术检测细胞行为。然后，测量葡萄糖和乳酸水平以评估糖酵解。接下来，利用RIP、MeRIP和qRT-PCR分析ALYREF与杆状病毒IAP repeat containing 5 （BIRC5）的相互作用。最后，通过构建异种移植肿瘤模型，证实了ALYREF和BIRC5在体内的作用。结果salyref在OC组织和细胞中均有高表达。下调ALYREF可减轻细胞增殖、迁移、侵袭、细胞周期和糖酵解，促进细胞凋亡。此外，ALYREF与BIRC5存在结合位点，且两者在肿瘤中的表达呈正相关。由于ALYREF下调而产生的抗肿瘤作用可以通过BIRC5的过表达而逆转。此外，ALYREF敲低抑制OC在体内的生长。结论alyref通过m5C修饰调控BIRC5 mRNA，在OC中发挥致癌作用。

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ALYREF regulates the m5C modification and stability of BIRC5 mRNA to promote ovarian cancer progression

Background

Ovarian cancer (OC) is the most dangerous cancer among gynecological tumors, which poses a significant threat to women’s health worldwide. 5-methylcytosine (m5C) plays a significant role in regulating tumor development. The RNA methyltransferase Aly/REF export factor (ALYREF) is one of the m5C-modified RNA-reading proteins. Although it was reported that ALREF played a facilitating role in a variety of cancers, the mechanism of ALYREF in OC was unclear.

Methods

Bioinformatics and western blot were applied to analyze the expression levels of ALYREF both in tissues and cells of OC. Cellular behaviors were detected by CCK8, colony formation assay, EdU assay and flow cytometry. Then, glucose and lactate levels were measured to assess glycolysis. Next, RIP, MeRIP and qRT-PCR were used to explore the interaction between ALYREF and baculoviral IAP repeat containing 5 (BIRC5). At last, the roles of ALYREF and BIRC5 in vivo were proved by constructing xenograft tumor models.

Results

ALYREF was highly expressed both in tissues and cells of OC. Downregulated ALYREF alleviated cell proliferation, migration, invasion, cell cycle, and glycolysis, and promoted apoptosis. Moreover, ALYREF had binding sites with BIRC5, and their expressions in tumors were positively correlated. The anti-tumor effects due to the downregulation of ALYREF could be reverted by overexpression of BIRC5. Furthermore, ALYREF knockdown restrained the growth of OC in vivo.

Conclusion

ALYREF regulates BIRC5 mRNA by m5C modification and exerts oncogenic effects in OC.

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.