低氧在肿瘤微环境中通过影响细胞增殖、代谢、凋亡、DNA修复以及化疗抗性等方面发挥着关键作用。由于低氧诱使了微小RNA的显著变化，因此有必要阐明每种低氧诱导小RNA对癌症进展的相对贡献。本研究旨在揭示在胰腺和乳腺癌进展中参与的低氧诱导小RNA，以突出新疗法开发的新靶点。 在20个周期内，MCF7乳腺癌细胞和PANC-1胰腺癌细胞分别经历了慢性周期性低氧，即连续72小时的缺氧后接24小时的复氧。通过RT-PCR阵列分析探究低氧引起的miRNA表达差异，并在可视化分析平台上进行进一步分析。MTT细胞增殖实验用于确定低氧细胞对阿霉素的化疗抗性。 慢性周期性低氧下，低氧的PANC-1细胞与其缺氧对照显示了相似的倍增时间，而低氧的MCF7细胞则与其缺氧对照相比呈现出显著的倍增时间增加。两种低氧细胞系都出现了类上皮间质转化（EMT）的表型特征，并具有阿霉素抗性。根据miRNet的研究结果，在第10个和第20个周期的低氧背景下，有6个和10个miRNA分别在富集了6个胰腺癌标志物的同时发挥了重要作用，而有7个和11个miRNA分别在富集了4个乳腺癌标志物的同时发挥了重要作用。miR-221、miR-21、miR-155和miR-34在第10个周期和第20个周期被发现参与增强低氧PANC-1胰腺癌标志物，而miR-93、miR-20a、miR-15和miR-17在第10个周期和第20个周期被发现参与增强低氧MCF7乳腺癌标志物。这种miRNA表达变化还与EMT样表型的出现、增殖率的变化和阿霉素抗性有关。化疗敏感性结果显示，慢性周期性低氧对于胰腺和乳腺癌细胞中产生化疗抗性表型至关重要。在20个周期的慢性周期性低氧后，PANC1中miR-181a和let-7e的表达差异以及MCF7中miR-93、miR-34和miR-27的表达差异可能与化疗抗性MCF7和PANC-1细胞的形成有关。然而，由于这些过程的具体机制尚不清楚，需要进一步研究。 版权所有 © 2023 Al-Sisan、Zihlif和Hammad。

Hypoxia plays a critical role in the tumor microenvironment by affecting cellular proliferation, metabolism, apoptosis, DNA repair, and chemoresistance. Since hypoxia provokes a distinct shift of microRNA, it is important to illustrate the relative contribution of each hypoxamiR to cancer progression.The present study aims to shed light on the hypoxamiRs that are involved in pancreatic and breast cancer progression to highlight novel targets for the development of new therapies.For 20 cycles, MCF7 breast cancer cells and PANC-1 pancreatic cancer cells were subjected to chronic cyclic hypoxia, which consisted of 72 hours of hypoxia followed by 24 hours of reoxygenation. After 10 and 20 cycles of hypoxia, miRNA expression alterations were profiled using RT-PCR array and further analyzed using a visual analytics platform. The MTT cell proliferation assay was used to determine hypoxic cells' chemoresistance to doxorubicin.Under chronic cyclic hypoxia, hypoxic PANC-1 cells have a comparable doubling time with their normoxic counterparts, whereas hypoxic MCF7 cells show a massive increase in doubling time when compared to their normoxic counterparts. Both hypoxic cell lines developed EMT-like phenotypes as well as doxorubicin resistance. According to the findings of miRNet, 6 and 10 miRNAs were shown to play an important role in enriching six hallmarks of pancreatic cancer in the 10th and 20th cycles of hypoxia, respectively, while 7 and 11 miRNAs were shown to play an important role in enriching the four hallmarks of breast cancer in the 10th and 20th cycles of hypoxia, respectively.miR-221, miR-21, miR-155, and miR-34 were found to be involved in the potentiation of hypoxic PANC-1 hallmarks at both the 10th and 20th cycles, while miR-93, miR-20a, miR-15, and miR-17 were found to be involved in the potentiation of hypoxic MCF7 hallmarks at both the 10th and 20th cycles. This variation in miRNA expression was also connected to the emergence of an EMT-like phenotype, alterations in proliferation rates, and doxorubicin resistance. The chemosensitivity results revealed that chronic cyclic hypoxia is critical in the formation of chemoresistant phenotypes in pancreatic and breast cancer cells. miR-181a and let-7e expression disparities in PANC1, as well as miR-93, miR-34, and miR-27 expression disparities in MCF7, may be associated with the formation of chemoresistant MCF7 and PANC-1 cells following 20 cycles of chronic cyclic hypoxia. Indeed, further research is needed since the particular mechanisms that govern these processes are unknown.Copyright © 2023 Al-Sisan, Zihlif and Hammad.