KIFC1通过调节PI3K/AKT信号通路促进胆管癌恶性生物学行为的实验研究-东南大学学报医学版

KIFC1通过调节PI3K/AKT信号通路促进胆管癌恶性生物学行为的实验研究

单位：1. 南京医科大学附属常州市第二人民医院普外科, 江苏常州 213003;
2. 南京医科大学附属常州市第二人民医院肿瘤科, 江苏常州 213003

分类号：R735.7

出版年·卷·期（页码）：2021·40·第三期（277-284）

摘要：

目的：探讨激肽家族成员C1（KIFC1）在胆管癌中的表达与作用及其调控机制。方法：通过GEPIA数据库探究胆管癌组织和正常组织中KIFC1的表达，采用实时定量PCR方法验证。实验选择人RBE和9810细胞，采用细胞计数试剂盒-8法检测细胞活力，采用Transwell检测细胞迁移和侵袭能力。采用FITC/PI法检测细胞凋亡。用蛋白质印迹法分析蛋白表达的变化。结果：KIFC1在胆管癌组织中的表达明显高于非肿瘤组织。KIFC1高表达可能与胆管癌预后不良有关。抑制KIFC1可能通过影响PI3K/AKT通路降低胆管癌细胞的增殖、迁移和转移能力，并促进细胞凋亡。结论：KIFC1可促进胆管癌的恶性生物学行为进展，其机制可能与KIFC1调控PI3K/AKT通路相关。KIFC1可能成为指导胆管癌诊断和治疗的潜在靶点。

Objective: To investigate the expressions and role of kinesin family member C1(KIFC1) in cholangiocarcinoma and its regulatory mechanism. Methods: The expression of KIFC1 in cholangiocarcinoma and normal tissues were investigated by GEPIA database. Real-time quantitative PCR(qRT-PCR) was used to verify the results. Experiments were carried out with human RBE and 9810 cells. CCK-8 assay was used to detect cell viability. Transwell was used to detect the ability of cell migration and invasion. Apoptosis was detected by FITC/PI assay. Western blot assay was used to analyze the changes of protein expression. Results: The results demonstrated the expression of KIFC1 was significantly higher in cholangiocarcinoma tissues than that in non-tumor tissues.The high expression of KIFC1 may be related to the poor prognosis of cholangiocarcinoma. The down-regulation of KIFC1 may inhibit the proliferation, migration and metastasis of cholangiocarcinoma cells and promote apoptosis by regulating PI3K/AKT pathway. Conclusion: KIFC1 promotes the malignant biological progress of cholangiocarcinoma, and its mechanism may be related to the regulation of PI3K/AKT pathway by KIFC1. KIFC1 may be a potential target to guide the diagnosis and treatment of cholangiocarcinoma.

参考文献：

[1] RIZVI S, GORES G J.Pathogenesis, diagnosis, and management of cholangiocarcinoma[J]. Gastroenterology, 2013, 145:1215-1229.
[2] JARNAGIN W R, FONG Y, DEMATTEO R P, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma[J]. Ann Surg, 2001, 234:507-517.
[3] BARR FRITCHER E G, VOSS S J, BRANKLEY M S, et al. An optimized set of fluorescence in situ hybridization probes for detection of pancreatobiliary tract cancer in cytology brush samples[J]. Gastroenterology, 2015, 149:1813-1824.
[4] GONDA T A, VITERBO D, GAUSMAAN V, et al. Mutation profile and fluorescence in situ hybridization analyses increase detection of malignancies in biliary strictures[J]. Clin Gastroenterol Hepatol, 2017, 15:913-919.
[5] VALLE J, WASAN H, PALMER H D, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med, 2010, 362:1273-1281.
[6] YU K M, HOU L, ZHU J Q, et al. KIFC1 participates in acrosomal biogenesis, with discussion of its importance for the perforatorium in the Chinese mitten crab Eriocheir sinensis[J]. Cell Tissue Res, 2009, 337:113-123.
[7] NATH S, BANANIS E, SARKAR S, et al. Kif5B and Kifc1 interact and are required for motility and fission of early endocytic vesicles in mouse liver[J]. Mol Biol Cell, 2007, 18:1839-1849.
[8] PAWAR S, DONTHAMSETTY S, PANNU V, et al. KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas:delineating protein interaction networks and signaling circuitries[J]. J Ovarian Res, 2014, 7:53.
[9] OUE N, MUKAI S, LMAI T, et al. Induction of KIFC1 expression in gastric cancer spheroids[J]. Oncol Rep, 2016, 36:349-355.
[10] LI Y, LU W, CHEN D, et al. KIFC1 is a novel potential therapeutic target for breast cancer[J]. Cancer Biol Ther, 2015, 16:1316-1322.
[11] GRINBERG-RASHI H, OFEK E, PERELMAN M, et al. The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain[J]. Clin Cancer Res, 2009, 15:1755-1761.
[12] YU Y, FENG Y.The role of kinesin family proteins in tumorigenesis and progression:potential biomarkers and molecular targets for cancer therapy[J]. Cancer, 2010, 116(22):5150-5160.
[13] RIZVI S, KHAN A S, HALLEMEIER L C, et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol, 2018, 15(2):95-111.
[14] DANIAL N N, KORSMEYER J S.Cell death:critical control points[J]. Cell, 2004, 116(2):205-19.
[15] HANAHAN D, WEINBERG A R.Hallmarks of cancer:the next generation[J]. Cell 2011, 144(5):646-674.
[16] PARVIN A, HAO S, TAN F, et al. Inhibition of kinesin motor protein KIFC1 by AZ82 induces multipolar mitosis and apoptosis in prostate cancer cell[J]. Gene, 2020, 760:144-989.
[17] ZHANG C, CHEN X, CHEN X, et al. miR-135a acts as a tumor suppressor in gastric cancer in part by targeting KIFC1[J]. Onco Targets Ther, 2016, 15(9):3555-3563.
[18] FU X, ZHU Y, ZHENG B, et al. KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma[J]. Int J Oncol, 2018, 52(6):1912-1922.
[19] ZHOU K, ZHAO J, QI L, et al. Kinesin family member C1(KIFC1) accelerates proliferation and invasion of endometrial cancer cells through modulating the PI3K/AKT signaling pathway[J]. Technol Cancer Res Treat, 2020, 19:1533033820964217.
[20] HAN J, WANG F, LAN Y, et al. KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling[J]. Oncogene, 2019, 38(3):406-420.
[21] FU X, LIU M, QU S, et al. Exosomal microRNA-32-5p induces multidrug resistance in hepatocellular carcinoma via the PI3K/Akt pathway[J]. Journal of Experimental & Clinical Cancer Research, 2018, 37(1):52.
[22] DAVID J M, DOMINGUEZ C, PALENA C.Pharmacological and immunological targeting of tumor mesenchymalization[J]. Pharmacol Therapeut, 2017, 170:212-225.

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