Down-regulation of miR-30a-5p is Associated with Poor Prognosis and Promotes Chemoresistance of Gemcitabine in Pancreatic Ductal Adenocarcinoma
Down-regulation of miR-30a-5p is Associated with Poor Prognosis and Promotes Chemoresistance of Gemcitabine in Pancreatic Ductal Adenocarcinoma
复制标题
miR-30a-5p 下调与胰腺导管腺癌预后不良相关，并促进吉西他滨化疗耐药
DOI：
10.7150/jca.31191
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Cao, Liping
中科院分区：
文献类型：
--
作者：
Zhou, Liangjing;Jia, Shengnan;Cao, Liping
microRNA-30 a-5 p（miR-30 a-5 p）在许多生物学和病理学过程中起着重要作用，因此得到了广泛的研究。然而，其在胰腺导管腺癌（PDAC）中的表达和功能尚不清楚。此外，miR-30 a-5 p是否影响PDAC细胞对吉西他滨（GEM）的敏感性值得进一步探讨。结果显示，miR-30 a-5 p在胰腺癌中表达降低，表达下调与预后不良相关，而上调miR-30 a-5 p则抑制肿瘤细胞增殖、细胞周期和凋亡增加。胰腺癌吉西他滨耐药细胞和亲本胰腺癌细胞的miRNA表达谱显示miR-30 a-5 p表达显著变化。此外，上调PDAC中的miR-30 a-5 p显著增加吉西他滨的化疗敏感性。此外，FOXD 1是miR-30 a-5 p的直接靶点，miR-30 a-5 p/FOXD 1/ERK轴可能在胰腺癌吉西他滨耐药的发展中发挥重要作用。总之，我们的研究表明miR-30 a-5 p增加了胰腺癌对吉西他滨的敏感性，它可能是克服吉西他滨耐药的潜在治疗靶点。
MicroRNA-30a-5p (miR-30a-5p) plays an important role in many biological and pathological processes, and therefore has been studied extensively. However, its expression and function in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Furthermore, whether miR-30a-5p affects sensitivity of PDAC cells to gemcitabine (GEM) is worthy of further exploration. The results showed that miR-30a-5p expression in pancreatic cancer was decreased and the down-regulated expression correlated with poor prognosis, while up-regulating miR-30a-5p suppressed tumor cell proliferation, cell cycle and increased apoptosis. MiRNA expression profiles between gemcitabine-resistant pancreatic cancer cells and parental pancreatic cancer cells showed significant change of miR-30a-5p expression. Besides, up-regulating miR-30a-5p in PDAC significantly increased the chemosensitivity of gemcitabine. Furthermore, FOXD1 is a direct target of miR-30a-5p and the miR-30a-5p/FOXD1/ERK axis may play an important role in the development of gemcitabine resistance in pancreatic cancer. In summary, our study showed that miR-30a-5p increases the sensitivity of pancreatic cancer to gemcitabine, and it may be a potential therapeutic target to overcome gemcitabine resistance.