circFNDC3B通过miR-370-3p/miR-136-5p靶向MYO5A促进食管鳞状细胞癌的进展。
circFNDC3B promotes esophageal squamous cell carcinoma progression by targeting MYO5A via miR-370-3p/miR-136-5p.
发表日期:2023 Sep 04
作者:
Dan Song, Ziqi Ye, Fangyu Chen, Liangliang Zhan, Xinchen Sun
来源:
Cellular & Molecular Immunology
摘要:
食管鳞癌(ESCC)是全球常见的恶性肿瘤。环状RNA(circRNA)在肿瘤发生发展中具有重要价值。然而,circFNDC3B在ESCC中的机制有待阐明。首先,通过对Actinomycin D和RNase R的测量评估了circFNDC3B的环特性。通过CCK-8、EdU和流式细胞术检查了circFNDC3B在ESCC细胞中的功能。随后,使用荧光素酶报告基因检测解释了circFNDC3B的分子机制。最后,我们构建了异种移植模型以证明circFNDC3B在体内的作用。我们的研究发现circFNDC3B比其线性RNA更稳定,并在ESCC中明显上调。功能研究结果表明,沉默circFNDC3B可减少ESCC细胞的增殖并增强细胞凋亡作用。同时,circFNDC3B的敲低减轻了体内肿瘤的进展。接下来,发现miR-370-3p/miR-136-5p与circFNDC3B结合。miR-370-3p/miR-136-5p逆转了circFNDC3B对细胞增殖的促进作用和对细胞凋亡的抑制作用。MYO5A是miR-370-3p/miR-136-5p的下游靶标。circFNDC3B作为miR-370-3p/miR-136-5p的海绵缓解了miR-370-3p/miR-136-5p对MYO5A的抑制作用,从而加速了ESCC的进展。circFNDC3B通过吸附miR-370-3p/miR-136-5p而正调节MYO5A的表达,从而在ESCC中具有促癌效应。circFNDC3B是ESCC的潜在诊断标志物。© 2023. BioMed Central Ltd., part of Springer Nature.
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor worldwide. Circular RNA (circRNA) is of great value in tumorigenesis progression. However, the mechanism of circFNDC3B in ESCC remains to be clarified.Firstly, the circular characteristics of circFNDC3B were evaluated by Actinomycin D and RNase R measurements. The functions of circFNDC3B in ESCC cells were examined by CCK-8, EdU and flow cytometry. Subsequently, the molecular mechanism of circFNDC3B was explained using luciferase reporter gene detection. Finally, we constructed xenograft model to prove the role of circFNDC3B in vivo.Our study revealed that circFNDC3B was more stable than its linear RNA and prominently upregulated in ESCC. Functional findings suggested that silencing of circFNDC3B reduced the proliferation and enhanced apoptosis of ESCC cells in vitro. Meanwhile, knockdown of circFNDC3B attenuated tumor progression in vivo. Next, miR-370-3p/miR-136-5p was discovered to bind circFNDC3B. miR-370-3p/miR-136-5p reversed the promotive effect on cell proliferation and the inhibitory effect on cell apoptosis of circFNDC3B. MYO5A was a downstream target of miR-370-3p/miR-136-5p. CircFNDC3B served as a sponge for miR-370-3p/miR-136-5p and alleviated the prohibitory effect of miR-370-3p/miR-136-5p on MYO5A, which accelerated ESCC progression.circFNDC3B positively adjusted the MYO5A expression via spongy miR-370-3p/miR-136-5p, hence achieving the cancer-promoting effect on ESCC. circFNDC3B was a prospective diagnosis marker for ESCC.© 2023. BioMed Central Ltd., part of Springer Nature.