Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation.
Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation.
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DOI：
10.1111/cas.13610
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发表时间：
2018-06
期刊：
影响因子：
5.7
通讯作者：
Natsugoe S
中科院分区：
文献类型：
--
作者：
Idichi T;Seki N;Kurahara H;Fukuhisa H;Toda H;Shimonosono M;Okato A;Arai T;Kita Y;Mataki Y;Kijima Y;Maemura K;Natsugoe S
我们之前使用 RNA 测序来建立胰腺导管腺癌 (PDAC) 的 microRNA (miRNA) 表达特征。我们发现前 miR-148a 的两条链（miR-148a-5p：过客链和 miR-148a-3p：引导链）在癌症组织中均下调。 miR-148a-5p 和 miR-148a-3p 的异位表达显着抑制癌细胞迁移和侵袭，表明 pre-miR-148a 的两条链在 PDAC 细胞中均具有肿瘤抑制作用。计算机数据库和全基因组基因表达分析总共鉴定了 15 个基因，这些基因是这些 miRNA 调节的推定靶标。 miR-148a-5p 靶标（PHLDA2、LPCAT2 和 AP1S3）和 miR-148a-3p 靶标（SMA、ENDOD1 和 UHMK1）的高表达与 PDAC 患者的不良预后相关。此外，PHLDA2表达的敲低抑制了癌细胞的侵袭性，表明PHLDA2在PDAC细胞中充当癌基因。前 miR-148a (miR-148-5p) 过客链的参与是癌症研究中的一个新概念。识别致死性 PDAC 中肿瘤抑制 miRNA 调控网络的新方法可能为这种疾病提供新的预后标志物和治疗靶点。
We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre‐miR‐148a (miR‐148a‐5p: the passenger strand and miR‐148a‐3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR‐148a‐5p and miR‐148a‐3p significantly inhibited cancer cell migration and invasion, indicating that both strands of pre‐miR‐148a had tumor‐suppressive roles in PDAC cells. In silico database and genome‐wide gene expression analyses identified a total of 15 genes that were putative targets regulated by these miRNAs. High expression of miR‐148a‐5p targets (PHLDA2,LPCAT2 and AP1S3) and miR‐148a‐3p targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement of the passenger strand of pre‐miR‐148a (miR‐148‐5p) is a new concept in cancer research. Novel approaches that identify tumor‐suppressive miRNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.
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影响因子：
3.8
作者：
Anaya, Jordan
通讯作者：
Anaya, Jordan
肿瘤抑制的microRNA-29s通过靶向头部和颈部鳞状细胞癌中的层粘连蛋白 - 整合蛋白信号传导来抑制癌细胞的迁移和侵袭。
影响因子：
8.8
作者：
Kinoshita, T.;Nohata, N.;Hanazawa, T.;Kikkawa, N.;Yamamoto, N.;Yoshino, H.;Itesako, T.;Enokida, H.;Nakagawa, M.;Okamoto, Y.;Seki, N.
通讯作者：
Seki, N.
影响因子：
3.5
作者：
Fuse, Miki;Kojima, Satoko;Seki, Naohiko
通讯作者：
Seki, Naohiko
影响因子：
3.1
作者：
Cordeiro, Amilcar;Paula Neto, Ana;Doria, Sofia
通讯作者：
Doria, Sofia
影响因子：
8.8
作者：
Goto Y;Kurozumi A;Arai T;Nohata N;Kojima S;Okato A;Kato M;Yamazaki K;Ishida Y;Naya Y;Ichikawa T;Seki N
通讯作者：
Seki N