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Abstract：
BACKGROUND: At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism.
METHODS: We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo.
RESULTS: According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC.
CONCLUSIONS: In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.
METHODS: We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo.
RESULTS: According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC.
CONCLUSIONS: In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.
摘要：
背景：目前，已经发现许多患者对放射治疗产生了抗性，大大降低了放疗的效果,进而影响预后。CircRNAs参与多种肿瘤细胞放射敏感性的调节。因此,本研究的主要目的是探讨CircRNA_101491对ESCC放射敏感性的调节作用及其相关机制。
方法：我们通过梯度剂量法建立了ESCC耐辐射细胞系（KYSE150R细胞），并在体外测试了KYSE150R细胞与亲本细胞之间KYSE150的差异。然后，在敲除CircRNA_101491的表达后，进行了一系列体外实验，以验证CircRNA_101491对KYSE150R细胞表型和放射敏感性的影响，并进一步分析了相关的监管机制。此外,我们还使用裸鼠移植瘤模型来研究CircRNA_101491对ESCC体内放射敏感性的影响。
结果：根据一系列体外实验，我们证实KYSE150R细胞失去上皮表型，获得间质细胞样表型，发现CircRNA_101491在KYSE150R细胞中高表达。此外,我们发现，敲低CircRNA_101491的表达将解除miR-125a-5p的抑制，然后逆转EMT的过程，加速细胞凋亡的过程，从而在放射增敏中发挥作用。裸鼠移植瘤的体内实验还表明，敲低CircRNA_101491的表达可以增强ESCC的放射敏感性。
结论：结论：我们证实干扰CircRNA_101491的表达可以减轻miR-125a-5p的抑制,从而逆转间质表型的过程，加速细胞凋亡的过程，增强ESCC的放射敏感性。
方法：我们通过梯度剂量法建立了ESCC耐辐射细胞系（KYSE150R细胞），并在体外测试了KYSE150R细胞与亲本细胞之间KYSE150的差异。然后，在敲除CircRNA_101491的表达后，进行了一系列体外实验，以验证CircRNA_101491对KYSE150R细胞表型和放射敏感性的影响，并进一步分析了相关的监管机制。此外,我们还使用裸鼠移植瘤模型来研究CircRNA_101491对ESCC体内放射敏感性的影响。
结果：根据一系列体外实验，我们证实KYSE150R细胞失去上皮表型，获得间质细胞样表型，发现CircRNA_101491在KYSE150R细胞中高表达。此外,我们发现，敲低CircRNA_101491的表达将解除miR-125a-5p的抑制，然后逆转EMT的过程，加速细胞凋亡的过程，从而在放射增敏中发挥作用。裸鼠移植瘤的体内实验还表明，敲低CircRNA_101491的表达可以增强ESCC的放射敏感性。
结论：结论：我们证实干扰CircRNA_101491的表达可以减轻miR-125a-5p的抑制,从而逆转间质表型的过程，加速细胞凋亡的过程，增强ESCC的放射敏感性。
