上调的长非编码 RNA LINC01296 通过影响 EMT 预示着胰腺导管腺癌的预后不良，并促进细胞转移特性。

Upregulated long noncoding RNA LINC01296 indicates a dismal prognosis for pancreatic ductal adenocarcinoma and promotes cell metastatic properties by affecting EMT.

机构信息

Department of Gastrointestinal Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong Province, China.

Department of Gastroenterology, Yidu Central Hospital of Weifang, Qingzhou, Shandong Province, China.

出版信息

J Cell Biochem. 2019 Jan;120(1):552-561. doi: 10.1002/jcb.27411. Epub 2018 Sep 11.

DOI:10.1002/jcb.27411

PMID:30203487

Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to chemotherapy and radiotherapy and whose incidence has increased worldwide. Long noncoding RNAs have been demonstrated to play important roles in cancer initiation and progression. Long intergenic non-coding RNA 01296 (LINC01296) has been reported to be upregulated in several malignancies, but the clinical relevance and biological role of LINC01296 in PDAC are still unclear.

METHODS

RT-qPCR was performed to evaluate the expression of LINC01296 in 85 pared PDAC tissue samples and a panel of PDAC cell lines. The clinical value and prognostic role of LINC01296 in patients with PDAC were further explored. Furthermore, we explored the functional roles of LINC01296 depletion in PANC-1 and SW1990 cells, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT).

RESULTS

LINC01296 was enhanced in PDAC tissues and cell lines, and this overexpression was correlated with advanced tumor stages and positive lymph node metastasis in patients with PDAC. In addition, upregulation of LINC01296 was an independent prognostic predictor for patients with PDAC after surgery. Moreover, silencing of LINC01296 followed by treatment with small interfering RNAs suppressed cell proliferation and promoted cell apoptosis by affecting the Bcl-2/caspase-3 pathway. Importantly, LINC01296 attenuation impaired the migratory and invasive potential partly by reversing EMT.

CONCLUSIONS

Overall, our work may help to develop a novel prognostic biomarker and therapeutic target for PDAC.

摘要

背景

胰腺导管腺癌（PDAC）是一种致命的疾病，对化疗和放疗反应不佳，其发病率在全球范围内有所增加。长链非编码 RNA 已被证明在癌症的发生和发展中发挥重要作用。长基因间非编码 RNA 01296（LINC01296）已被报道在几种恶性肿瘤中上调，但 LINC01296 在 PDAC 中的临床相关性和生物学作用仍不清楚。

方法

采用 RT-qPCR 检测 85 对 PDAC 组织样本和一组 PDAC 细胞系中 LINC01296 的表达。进一步探讨 LINC01296 在 PDAC 患者中的临床价值和预后作用。此外，我们还研究了 LINC01296 耗竭在 PANC-1 和 SW1990 细胞中的功能作用，包括细胞增殖、凋亡、迁移、侵袭和上皮间质转化（EMT）。

结果

LINC01296 在 PDAC 组织和细胞系中表达增强，这种过表达与 PDAC 患者的晚期肿瘤分期和阳性淋巴结转移相关。此外，LINC01296 的上调是 PDAC 患者手术后的独立预后预测因子。此外，沉默 LINC01296 并用小干扰 RNA 处理可通过影响 Bcl-2/caspase-3 途径抑制细胞增殖并促进细胞凋亡。重要的是，LINC01296 的衰减部分通过逆转 EMT 来削弱迁移和侵袭潜能。