Molecular changes in adipocyte-derived stem cells during their interplay with cervical cancer cells
Molecular changes in adipocyte-derived stem cells during their interplay with cervical cancer cells
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DOI：
10.1007/s13402-021-00653-6
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发表时间：
2022-01-11
影响因子：
6.6
通讯作者：
Maldonado Lagunas，Vilma
中科院分区：
文献类型：
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作者：
Angelica De la Fuente-Hernandez，Marcela;Claudia Alanis-Manriquez，Erika;Maldonado Lagunas，Vilma
肥胖是一个重要的危险因素，至少在13种不同的肿瘤类型中与预后不良相关。这部分是由于肿瘤细胞和脂肪组织来源的干细胞（ADSC）之间的细胞间通讯，这在肥胖个体中增加。然而，到目前为止，人们对这些条件下ADSC中发生的分子变化知之甚少。宫颈癌在发展中国家妇女中的发病率和死亡率很高，特别是在那些高体重指数（BMI）的人中。MethodsWe分析了与宫颈癌细胞共培养的ADSCs的表达谱，通过大量RNA测序，然后评估由修饰的转录组引起的各种功能改变。在与HeLa细胞共培养后，在ADSC中鉴定了编码失调的RNA（在CaSki和SiHA细胞中验证）。随后的网络分析表明，这些变化与迁移，干性，DNA修复和细胞因子的产生相关。功能实验显示，与HeLa细胞共培养后，ADSCs的ALDHhigh亚群增加，迁移能力增强。有趣的是，发现CXCL 3及其基因内长非编码RNA lnc-CXCL 3在共培养期间被共调节。一个功能丧失的分析表明，lnc-CXCL 3作为一个关键的调节CXCL 3 expressions.ConclusionsOur结果表明，ADSCs和宫颈癌细胞之间的细胞间通信修改的RNA表达谱在前者，包括lncRNA，这反过来又可以调节不同的趋化因子，有利于恶性相关的能力，如迁移的表达。
PurposeObesity is as an important risk factor and has been associated with a worse prognosis in at least 13 distinct tumor types. This is partially due to intercellular communication between tumor cells and adipose tissue-derived stem cells (ADSCs), which are increased in obese individuals. As yet, however, little is known about the molecular changes occurring in ADSCs in these conditions. Cervical cancer has a high incidence and mortality rate in women from developing countries, particularly in those with a high body mass index (BMI).MethodsWe analyzed the expression profile of ADSCs co-cultured with cervical cancer cells through massive RNA sequencing followed by evaluation of various functional alterations resulting from the modified transcriptome.ResultsA total of 761 coding and non-coding dysregulated RNAs were identified in ADSCs after co-culture with HeLa cells (validation in CaSki and SiHA cells). Subsequent network analysis showed that these changes were correlated with migration, stemness, DNA repair and cytokine production. Functional experiments revealed a larger ALDHhighsubpopulation and a higher migrative capacity of ADSCs after co-culture with HeLa cells. Interestingly, CXCL3 and its intragenic long-noncoding RNA, lnc-CXCL3, were found to be co-regulated during co-culture. A loss-of-function assay revealed that lnc-CXCL3 acts as a key regulator of CXCL3 expression.ConclusionsOur results suggest that intercellular communication between ADSCs and cervical cancer cells modifies the RNA expression profile in the former, including that of lncRNAs, which in turn can regulate the expression of diverse chemokines that favor malignancy-associated capacities such as migration.