切换至 "中华医学电子期刊资源库"
高级检索
中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 269 -272. doi: 10.3877/cma.j.issn.1674-0793.2021.04.006

论著

BANCR调控VEGF-C/VEGFR-3通路促进胰腺癌微淋巴管生成
郝少龙1, 韩威1,†(), 纪宇1, 孙浩2, 石浩伟1, 马纪红3   
  1. 1. 101149　北京，首都医科大学附属北京潞河医院普外科
    2. 101149　北京，首都医科大学附属北京潞河医院中心实验室
    3. 101149　北京，首都医科大学附属北京潞河医院医疗保健病区
  • 收稿日期:2020-12-10 出版日期:2021-08-03
  • 通信作者: 韩威
  • 基金资助:
    北京市通州区科委科技创新专项(KJ2019CX014-05); 北京市通州区科技计划项目(KJ2020 CX006-10)

BANCR promoting lymphangiogenesis by regulating VEGF-C/VEGFR-3 pathway in pancreatic cancer

Shaolong Hao1, Wei Han1,†(), Yu Ji1, Hao Sun2, Haowei Shi1, Jihong Ma3   

  1. 1. Department of General Surgery, the Affiliated Beijing Luhe Capital University of Medical Sciences, Beijing 101149, China
    2. Department of Central Laboratory, the Affiliated Beijing Luhe Capital University of Medical Sciences, Beijing 101149, China
    3. Department of Health Care Ward, the Affiliated Beijing Luhe Capital University of Medical Sciences, Beijing 101149, China
  • Received:2020-12-10 Published:2021-08-03
  • Corresponding author: Wei Han
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

郝少龙, 韩威, 纪宇, 孙浩, 石浩伟, 马纪红. BANCR调控VEGF-C/VEGFR-3通路促进胰腺癌微淋巴管生成[J]. 中华普通外科学文献(电子版), 2021, 15(04): 269-272.

Shaolong Hao, Wei Han, Yu Ji, Hao Sun, Haowei Shi, Jihong Ma. BANCR promoting lymphangiogenesis by regulating VEGF-C/VEGFR-3 pathway in pancreatic cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(04): 269-272.

目的

研究BANCR在胰腺癌中的表达及其对淋巴管生成作用机制。

方法

实时荧光定量PCR（qPCR）检测胰腺癌细胞（SW1990、PANC-1）及人胰腺导管上皮细胞（HPDC）中BANCR的表达；应用siRNA干扰胰腺癌细胞BANCR的表达，将转染后的胰腺癌细胞与人真皮淋巴管内皮细胞（HDLEC）进行3D共培养，并统计微淋巴管密度（MLVD）。应用qPCR检测转染后的BANCR-siRNA组和空载质粒NC组胰腺癌细胞中VEGF-C、VEGFR-3 mRNA的相对表达量。

结果

与HPDC的1.02±0.222相比，胰腺癌细胞PANC-1和SW1990中BANCR显著高表达，分别为10.03±3.356、10.37±1.459（P<0.001）。干扰BANCR表达后BANCR-siRNA组的胰腺癌细胞MLVD较NC组显著降低（SW1990：3.87±1.767 vs 18.00±6.130，P<0.001；PANC-1：5.27±2.631 vs 16.80±3.764，P<0.001）。且BANCR-siRNA组中VEGF-C及VEGFR-3转录水平较NC组显著下调（VEGF-C：1.35±0.926 vs 6.97±3.677，P=0.011；VEGFR-3：0.98±0.635 vs 2.88±1.422，P=0.026）。

结论

BANCR在胰腺癌细胞中表达上调，并可能通过调控VEGF-C/VEGFR-3通路促进胰腺癌淋巴管生成和淋巴结转移，有望为胰腺癌的诊治提供新靶点。

关键词: 胰腺肿瘤, 长链非编码RNA, 淋巴管生成
Objective

To investigate the expression of BANCR in pancreatic carcinoma and its mechanism on lymphangiogenesis.

Methods

The expression of BANCR in pancreatic cancer cells (SW1990, PANC-1) and human pancreatic ductal epithelial cell (HPDC) was detected by qPCR. siRNA was used to interfere with the expression of BANCR in pancreatic cancer cells. The transfected pancreatic cancer cells and human dermal lymphatic endothelial cells (HDLEC) were co-cultured in 3D, and micro-lymphatic vessel density (MLVD) was calculated. qPCR was used to detect the relative expression of VEGF-C and VEGFR-3 mRNA in pancreatic cancer cells of BANCR-siRNA group and NC group.

Results

Compared with 1.02±0.222 of HPDC, the expression of BANCR in PANC-1 and SW1990 cells was significantly higher (10.03±3.356, 10.37±1.459, respectively) (P<0.001). The pancreatic cancer cell MLVD in the BANCR-siRNA group was significantly lower than that in the NC group (SW1990: 3.87±1.767 vs 18.00±6.130, P<0.001; PANC-1: 5.27±2.631 vs 16.80±3.764, P<0.001). And the transcriptional level of VEGF-C and VEGFR-3 in the BANCR-siRNA group was significantly lower than that in the NC group (VEGF-C: 1.35±0.926 vs 6.97±3.677, P=0.011; VEGFR-3: 0.98±0.635 vs 2.88±1.422, P=0.026).

Conclusion

BANCR is up-regulated in pancreatic carcinoma cells and may play an important role in lymphangiogenesis and lymph node metastasis in pancreatic carcinoma by regulating VEGF-C/VEGFR-3 pathway, which is expected to provide a new target for clinical diagnosis, treatment and prognosis of pancreatic carcinoma.

Key words: Pancreatic neoplasms, Long chain non-coding RNA, Lymphangiogenesis
表1 引物序列表
基因名称 上游引物 下游引物
BANCR 5’-GAGCCTTGCCAGTTCCATTT-3’ 5’-TGCAGAGGTGAGATTCAGGT-3’
GAPDH 5’-TCAAGAAGGTGGTGAAGCAGG-3’ 5’-TCAAAGGTGGAGGAGTGGGT-3’
BANCR siRNA 5’-GGUGTGGCGUCTUTUGCUUTT-3’ 5’-AAGCAAAAGACGCCACACCTT-3’
VEGF-C 5’-CTACAGATGTGGGGGTTGCT-3’ 5’-GATTGGCAAAACTGATTGTGAC-3’
VEGFR-3 5’-CTCTGACCTAGTGGAGATCCTG-3’ 5’-CTTCGGTGATATGTAGAGCTGTG-3’
图2 BANCR对胰腺癌细胞淋巴管生存的影响　A为胰腺癌细胞株PANC-1、SW1990中BANCR-siRNA与未经siRNA干扰的NC组淋巴管生成情况（×100）；B为几种细胞株中微淋巴管密度（MLVD）的比较；C为PC细胞株PANC-1、SW1990中BANCR表达与MLVD的相关性分析
图3 BANCR对胰腺癌细胞VEGF-C、VEGFR-3 mRNA的影响　BANCR-siRNA为干扰BANCR表达后胰腺癌细胞SW1990；NC为未经siRNA干扰的NC组；*两组VEGF-C相比，P<0.05；#两组VEGFR-3相比，P<0.05
[1]
Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014[J]. Chin J Cancer Res, 2018, 30(1): 1-12.
[2]
Kleeff J, Korc M, Apte M, et al. Pancreatic cancer[J]. Nat Rev Dis Primers, 2016, 2: 16022.
[3]
Schwarz RE, Smith DD. Extent of lymph node retrieval and pancreatic cancer survival: information from a large US population database[J]. Ann Surg Oncol, 2006, 13(9): 1189-1200.
[4]
Engreitz JM, Haines JE, Perez EM, et al. Local regulation of gene expression by lncRNA promoters, transcription and splicing[J]. Nature, 2016, 539(7629): 452-455.
[5]
Flockhart RJ, Webster DE, Qu K, et al. BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration[J]. Genome Res, 2012, 22(6): 1006-1014.
[6]
Fang S, Liu Z, Guo Q, et al. High BANCR expression is associated with worse prognosis in human malignant carcinomas: An updated systematic review and Meta-analysis[J]. BMC Cancer, 2020, 20(1): 870.
[7]
Fan YH, Ye MH, Wu L, et al. BRAF-activated lncRNA predicts gastrointestinal cancer patient prognosis: A Meta-analysis[J]. Oncotarget, 2017, 8(4): 6295-6303.
[8]
Shen X, Bai Y, Luo B, et al. Upregulation of lncRNA BANCR associated with the lymph node metastasis and poor prognosis in colorectal cancer[J]. Biol Res, 2017, 50(1): 32.
[9]
Zhou T, Gao Y. Increased expression of LncRNA BANCR and its prognostic significance in human hepatocellular carcinoma[J]. World J Surg Oncol, 2016, 14(1): 8.
[10]
刘子豪，杨同昕，徐志鹏, 等. 长链非编码RNA BANCR在食管鳞癌中的表达及对细胞增殖和侵袭能力的影响[J]. 现代生物医学进展, 2016, 16(24): 4622-4627.
[11]
Lou KX, Li ZH, Wang P, et al. Long non-coding RNA BANCR indicates poor prognosis for breast cancer and promotes cell proliferation and invasion[J]. Eur Rev Med Pharmacol Sci, 2018, 22(5): 1358-1365.
[12]
Zheng H, Xu J, Hao S, et al. Expression of BANCR promotes papillary thyroid cancer by targeting thyroid stimulating hormone receptor[J]. Oncol Lett, 2018, 16(2): 2009-2015.
[13]
Wu X, Xia T, Cao M, et al. LncRNA BANCR promotes pancreatic cancer tumorigenesis via modulating miR-195-5p/Wnt/β-Catenin signaling pathway[J]. Technol Cancer Res Treat, 2019, 18: 1533033819887962.
[14]
Cheng P, Jin G, Hu X, et al. Analysis of tumor-induced lymphangiogenesis and lymphatic vessel invasion of pancreatic carcinoma in the peripheral nerve plexus[J]. Cancer Sci, 2012, 103(10): 1756-1763.
[15]
Keklikoglou I, Hosaka K, Bender C, et al. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes[J]. Oncogene, 2015, 34(37): 4867-4878.
[16]
Ochi N, Matsuo Y, Sawai H, et al. Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis[J]. Pancreas, 2007, 34(4): 444-451.
[1] 朱韵莹, 高晓琳, 戈艳萍, 王张嵩, 林钊宇, 李劲松, 武东辉. 缺氧相关的长链非编码RNA LINC00970在唾液腺腺样囊性癌中的表达及其作用[J]. 中华口腔医学研究杂志(电子版), 2023, 17(03): 210-217.
[2] 贾成朋, 王代宏, 陈华, 孙备. 可切除性胰腺癌预后术前预测模型的建立及应用[J]. 中华普外科手术学杂志(电子版), 2023, 17(05): 566-570.
[3] 韩显林. 完全腹腔镜根治性胰十二指肠切除术（联合肠系膜上静脉切除人工血管重建）[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 133-133.
[4] 李泽乾, 郝少龙, 张博, 纪凯伦, 韩威. 外周血非编码RNA在胰腺癌中研究进展[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 217-220.
[5] 张太平, 翁桂湖, 刘悦泽. 不断推进中国腹腔镜胰腺癌手术规范化[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 120-123.
[6] 田锋, 郭俊超. 中国微创技术在胰腺癌手术中的应用现状和展望[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 124-128.
[7] 韩显林, 林伯铮, 洪夏飞. 腹腔镜胰腺癌手术研究进展及血管解剖要点[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 129-132.
[8] 毛永欢, 奚玲, 陆晨, 刘理想, 喻春钊, 沈晓菲. PI3K/Akt信号通路通过Plk1影响胰腺癌细胞PANC-1对吉西他滨的化疗敏感性[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 135-138.
[9] 李永宁, 付雪芹, 李英, 刘鹏, 刘松柏, 潘耀振. 基因相似序列家族成员126A靶向调控波形蛋白促进胰腺癌细胞侵袭和迁移及其机制[J]. 中华普外科手术学杂志(电子版), 2023, 17(02): 139-144.
[10] 唐国军, 洪余德, 赵崇玉, 李辽源. 基于TCGA数据库Wnt相关长链非编码RNA构建肾乳头状细胞癌预后模型[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 270-275.
[11] 王楚风, 蒋安. 原发性肝癌的分子诊断[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 499-503.
[12] 王迪, 吕少诚, 黄金灿, 潘飞, 姜涛, 郎韧. 肺腺癌胰腺转移伴门静脉侵犯一例[J]. 中华肝脏外科手术学电子杂志, 2023, 12(04): 457-460.
[13] 莫建涛, 杨沛泽, 曹瑞奇, 马清涌, 王铮, 仵正, 周灿灿. 基于生物信息学分析构建肝内胆管细胞癌患者铁死亡相关lncRNA预后模型[J]. 中华肝脏外科手术学电子杂志, 2023, 12(02): 185-189.
[14] 方蕊, 宋旭东. 非编码核糖核酸与白内障相关的研究进展[J]. 中华眼科医学杂志(电子版), 2023, 13(02): 94-98.
[15] 王健, 赵海剑, 孙静, 张晓雨, 陈柏羽. LncRNA SNHG4表达与结直肠癌预后的关系[J]. 中华消化病与影像杂志(电子版), 2023, 13(03): 139-144.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号