切换至 "中华医学电子期刊资源库"
高级检索
中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2021, Vol. 11 ›› Issue (05) : 262 -271. doi: 10.3877/cma.j.issn.2095-1221.2021.05.002

论著

p53诱导型核蛋白2通过活化β-连环蛋白促进乳腺癌细胞的侵袭转移
周源1, 董靖1, 陈亚希1, 谢阳1, 宁琳洪1,†()   
  1. 1. 401331，重庆医药高等专科学校临床医学院
  • 收稿日期:2021-03-19 出版日期:2021-10-01
  • 通信作者: 宁琳洪
  • 基金资助:
    校级科研项目(ygz2019302，ygz2019109); 重庆市科委基金(cstc2018jcyjAX0758)

P53-induced nuclear protein 2 promotes invasion and metastasis of breast cancer cells through activating β-catenin

Yuan Zhou1, Jing Dong1, Yaxi Chen1, Yang Xie1, LingHong Ning1,†()   

  1. 1. Department of Internal Medicine, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China
  • Received:2021-03-19 Published:2021-10-01
  • Corresponding author: LingHong Ning
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

周源, 董靖, 陈亚希, 谢阳, 宁琳洪. p53诱导型核蛋白2通过活化β-连环蛋白促进乳腺癌细胞的侵袭转移[J]. 中华细胞与干细胞杂志(电子版), 2021, 11(05): 262-271.

Yuan Zhou, Jing Dong, Yaxi Chen, Yang Xie, LingHong Ning. P53-induced nuclear protein 2 promotes invasion and metastasis of breast cancer cells through activating β-catenin[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2021, 11(05): 262-271.

目的

探讨p53诱导型核蛋白2 （TP53INP2）对乳腺癌细胞侵袭转移的影响。

方法

采用Transwell小室筛选出癌侵袭性（MDA-MB-231-M）和非侵袭性（MDA-MB-231-NM）乳腺癌细胞；采用脂质体转染技术将pCMV6-TP53INP2过表达重组载体质粒转染至MDA-MB-231-NM细胞中，归为OE-TP53INP2组；将pRS-sh-TP53INP2干扰载体质粒转染至MDA-MB-231-M细胞中，以此降低TP53INP2，归为sh-TP53INP2组。OE-TP53INP2组细胞中分别转染β-catenin干扰质粒、加入Wnt/β-catenin信号通路抑制剂（XAV-939），归为OE-TP53INP2+si-β-catenin组、OE-TP53INP2 + XAV-939组。荧光定量PCR （RT-qPCR）检测MDA-MB-231-NM和MDA-MB-231-M细胞中TP53INP2的表达，Transwell小室法检测MDA-MB-231-NM和MDA-MB-231-M细胞迁移和侵袭，TOPflash/FOPflash实验检测Wnt/β-catenin信号通路的活性，Western blot检测肿瘤蛋白TP53INP2和β-连环蛋白（β-catenin）、上皮标志物上皮型钙黏蛋白（E-cadherin）、间充质标志物神经型钙黏蛋白（N-cadherin）和波形蛋白（vimentin）的表达水平。两组的定量资料比较采用t检验，多组间比较采用单因素方差分析，组间两两比较采用SNK-q检验。

结果

与非侵袭性MDA-MB-231-NM细胞比较，侵袭性的MDA-MB-231-M细胞中N-cadherin、vimentin和TP53INP2的蛋白表达水平（1.00±0.10比3.15±0.07，1.00±0.07比2.35±0.06，1.00±0.04比2.13±0.07）均升高，E-cadherin的表达水平（1.00±0.06比0.37±0.05）降低，迁移和侵袭细胞数[（43.67±13.25）个比（154.33±15.05）个，（46.67±12.70）个比（162.33±16.50）个]增加，差异有统计学意义（P均< 0.001）。与对照组比较，过表达TP53INP2的MDA-MB-231-NM细胞中N-cadherin、vimentin和β-catenin的表达水平（1.00±0.06比1.85±0.07，1.00±0.07比2.14±0.04，1.00±0.11比3.63±0.05）均升高，E-cadherin的表达水平（1.00±0.05比0.43± 0.05）降低，迁移和侵袭细胞数[（118.00±12.45）个比（318.67±12.50）个，（81.67±12.87）个比（287.33±11.70）个]均升高，差异有统计学意义（P均< 0.001），干扰TP53INP2基因后得到相反的结果。与过表达TP53INP2组比较，过表达TP53INP2同时干扰β-catenin后，细胞中N-cadherin和vimentin的表达水平（2.65±0.07比0.46±0.05，4.23±0.08比2.34±0.04）均降低，E-cadherin的表达水平（0.24±0.04比1.12±0.08）升高，迁移和侵袭细胞数[（170.67±12.05）个比（62.00±8.82）个，（122.67±13.70）个比（76.00±12.82）个]均降低，差异有统计学意义（P均< 0.001），过表达TP53INP2同时加Wnt/β-catenin信号通路抑制剂（XAV-939）后得到类似的结果。

结论

TP53INP2通过激活Wnt/β-catenin信号通路从而调控E-cadherin、N-cadherin、vimentin蛋白的表达，进而促进乳腺癌细胞的侵袭转移。

关键词: p53诱导型核蛋白2, β-连环蛋白, 侵袭, 转移
Objective

To investigate the effect of tumor protein P53 inducible nuclear protein 2 (TP53INP2) on invasion and metastasis of breast cancer cells.

Methods

The invasive (MDA-MB-231-M) and non-invasive (MDA-MB-231-NM) breast cancer cells were screened by Transwell cell method. Then pCMV6-TP53INP2 overexpression recombinant vector plasmid was transfected into MDA-MB-231-NM cells as OE-TP53INP2 group, while pRS-sh-TP53INP2 interference vector plasmid was transfected into MDA-MB-231-M cells as sh-TP53INP2 group. Cells of OE- TP53INP2 group were transfected with β-catenin interference plasmid or Wnt/ β-catenin signaling pathway inhibitor (XAV-939) , which were divided into OE-TP53INP2+si-β-catenin group and OE-TP53INP2 + XAV-939 group respectively. Quantitative real-time PCR (RT-qPCR) was used to detect the expression of TP53INP2 in MDA-MB-231-NM and MDA-MB-231-M cells, and Transwell assay was used to detect the migration and invasion ability of MDA-MB-231-NM and MDA-MB-231-M cells, TOPflash/FOPflash experiment was used to detect the activity of Wnt/ β-catenin signaling pathway, and Western blot was used to detect the protein expression levels of TP53INP2, β-catenin, epithelial marker epithelial cadherin (E-cadherin) , mesenchyme markers N-cadherin and vimentin. The quantitative data of the two groups were compared through t-test. One-way analysis of variance was used to compare the difference among multiple groups, and SNK-q test was used to compare the difference between groups.

Results

Compared with non-invasive MDA-MB-231- NM cells, the protein expression levels of N-cadherin, vimentin and TP53INP2 in invasive MDA-MB-231-M cells were increased (1.00±0.10 vs 3.15±0.07, 1.00±0.07 vs 2.35 ± 0.06, 1.00±0.04 vs 2.13±0.07) , but the protein expression level of E-cadherin was decreased (1.00±0.06 vs 0.37±0.05) , and the difference was statistically significant (P < 0.001) ; at the same time, the number of migration and invasion of cells (43.67±13.25 vs 154.33±15.05, 46.67±12.70 vs 162.33±16.50) was significantly increased (P < 0.001) . Compared with the control group, the protein expression levels of N-cadherin, vimentin and β-catenin were increased in TP53INP2-overexpressed MDA-MB-231-NM cells (1.00±0.06 vs 1.85±0.07, 1.00±0.07 vs 2.14±0.04, 1.00±0.11 vs 3.63±0.05) , whereas the protein expression level of E-cadherin was decreased (0.43±0.05 vs 1.00±0.05) , and the difference was statistically significant (P < 0.001) ; And the number of migration and invasion of cells (118.00±12.45 vs 318.67±12.50, 81.67±12.87 vs 287.33±11.70) was significantly increased (P < 0.001) . But all the results were opposite after interference with the TP53INP2 gene. Meanwhile, compared with the TP53INP2 overexpression group, when TP53INP2 overexpression simultaneously interfered with β-catenin, the protein expression levels of N-cadherin and vimentin in cells were decreased (2.65±0.07 vs 0.46±0.05, 4.23±0.08 vs 2.34±0.04) , the protein expression level of E-cadherin was increased (0.24±0.04 vs 1.12±0.08), and the difference was statistically significant (P <0.001) ; and the number of migration and invasion of cells (62.00±8.82 vs 170.67±12.05, 76.00±12.82 vs 122.67±13.70) were significantly decreased (P < 0.001) . Interestingly, similar results were obtained after overexpression of TP53INP2 combined with Wnt/β-catenin signaling pathway inhibitor (XAV-939) .

Conclusion

TP53INP2 can regulate E-cadherin, N-cadherin, and vimentin proteins by activating the Wnt/β-catenin signaling pathway, thus promoting the invasion and metastasis of breast cancer cells.

Key words: TP53INP2, β-catenin, Invasion, Metastasis
表1 引物序列信息
基因 序列（5'→3'） 预期扩增产物长度（bp）
TP53INP2 上游TTCGTGTCGGAGGAGGATGAAG 143
  下游AACCAGCTCTCGTCCATCAAGG
β-actin 上游CACCATTGGCAATGAGCGGTTC 135
  下游AGGTCTTTGCGGATGTCCACGT
图1 侵袭性和非侵袭性MDA-MB-231细胞亚系分离示意图
图2 Western blot检测E-cadherin、N-cadherin和vimentin蛋白表达水平
图3 Transwell小室实验检测MDA-MB-231-NM和MDA-MB-231-M细胞的侵袭转移（结晶紫染色，×100）
表2 乳腺癌细胞系MDA-MB-231-NM和MDA-MB-231-M迁移和侵袭能力（ ± s）
分组 实验次数 细胞迁移数（个） 细胞侵袭数（个） E-cadherin N-cadherin vimentin
MDA-MB-231-NM 3 43.67±13.25 46.67±12.70 1.00±0.06 1.00±0.10 1.00±0.07
MDA-MB-231-M 3 154.33±15.05 162.33±16.50 0.37±0.05 3.15±0.07 2.35±0.06
t值   9.559 9.621 13.971 30.507 25.362
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
图4 Western blot检测TP53INP2蛋白表达水平
表3 MDA-MB-231-NM和MDA-MB-231-M细胞中TP53INP2 mRNA及蛋白的表达水平（ ± s）
分组 实验次数 TP53INP2 mRNA TP53INP2蛋白
MDA-MB-231-NM 3 1.37±0.11 1.00±0.04
MDA-MB-231-M 3 5.25±0.12 2.13±0.07
t值   41.283 24.276
P值   < 0.001 < 0.001
图5 Western blot检测TP53INP2过表达后E-cadherin、N-cadherin、vimentin蛋白的表达水平
图6 Transwell实验检测TP53INP2过表达后乳腺癌细胞MDA-MB-231-NM侵袭转移能力（结晶紫染色，×100）
表4 TP53INP2基因过表达后对MDA-MB-231-NM细胞侵袭转移的影响（ ± s）
分组 实验次数 细胞迁移数（个） 细胞侵袭数（个） TP53INP2 E-cadherin N-cadherin vimentin
对照 3 118.00±12.45 81.67±12.87 1.00±0.04 1.00±0.05 1.00±0.06 1.00±0.07
OE-TP53INP2 3 318.67±12.50 287.33±11.70 4.35±0.05 0.43±0.05 1.85±0.07 2.14±0.04
t值   19.701 20.541 90.618 13.962 15.969 24.491
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
图7 Western blot检测干扰TP53INP2后E-cadherin、N-cadherin、vimentin蛋白的表达水平
图8 Transwell实验检测干扰TP53INP2后乳腺癌细胞MDA-MB-231-M侵袭转移能力（结晶紫染色，×100）
表5 干扰TP53INP2基因后对MDA-MB-231-M细胞侵袭转移的影响（ ± s）
分组 实验次数 细胞迁移数（个） 细胞侵袭数（个） TP53INP2 E-cadherin N-cadherin vimentin
对照 3 262.337±12.05 214.33±12.05 1.00±0.04 1.00±0.05 1.00±0.04 1.00±0.04
sh-TP53INP2 3 60.33±12.50 46.67±13.94 0.41±0.03 1.97±0.06 0.38±0.05 0.33±0.05
t值   20.152 15.760 20.438 23.299 16.771 18.124
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
图9 TP53INP2能激活Wnt/β-catenin信号通路
表6 TP53INP2表达对Wnt/β-catenin、TGF-β/Smad和Notch信号通路的影响（ ± s）
分组 实验次数 TP53INP2 β-catenin Cleaved Notch Smad2 Smad3 Smad4
对照 3 1.00±0.07 1.00±0.11 1.00±0.06 1.00±0.11 1.00±0.05 1.00±0.05
OE-TP53INP2 3 3.13±0.06 3.63±0.05 1.13±0.09 1.20±0.13 0.94±0.06 1.06±0.08
t值   40.016 37.700 2.082 2.034 1.331 1.101
P值   < 0.001 < 0.001 0.106 0.112 0.254 0.332
对照 3 1.00±0.08 1.00±0.05 1.00±0.11 1.00±0.05 1.00±0.07 1.00±0.05
sh-TP53INP2 3 0.28±0.05 0.21±0.07 1.19±0.12 0.95±0.06 0.88±0.08 0.97±0.08
t值   13.219 15.906 2.022 1.109 1.955 0.551
P值   < 0.001 < 0.001 0.113 0.330 0.122 0.611
图10 Western blot检测过表达TP53INP2并干扰β-catenin后TP53INP2、β-catenin、E-cadherin、N-cadherin和vimentin蛋白的表达水平
图11 Transwell实验检测过表达TP53INP2并干扰β-catenin后乳腺癌细胞MDA-MB-231-M侵袭转移能力（结晶紫染色，×100）
图12 过表达TP53INP2并Wnt/β-catenin信号通路抑制剂（XAV-939）处理后乳腺癌细胞MDA-MB-231-M侵袭转移能力降低（结晶紫染色，×100）
图13 Western blot检测过表达TP53INP2并抑制剂（XAV-939）处理β-catenin后TP53INP2、β-catenin、E-cadherin、N-cadherin和Vimentin蛋白的表达水平
表7 TP53INP2通过Wnt/β-catenin影响细胞的侵袭转移（ ± s）
分组 实验次数 细胞迁移数（个） 细胞侵袭数（个） TP53INP2 β-catenin E-cadherin N-cadherin vimentin
对照 3 46.33±11.25 44.00±12.41 1.00±0.05 1.00±0.07 1.00±0.09 1.00±0.06 1.00±0.06
OE-TP53INP2 3 170.67±12.05a 122.67±13.70a 3.28±0.11a 7.13±0.12a 0.24±0.04a 2.65±0.07a 4.23±0.08a
OE-TP53INP2+ si-β-catenin 3 62.00±8.82b 76.00±12.82b 2.86±0.07b 3.46±0.08b 1.12±0.08b 0.46±0.05b 2.34±0.04b
F值   175.702 101.602 52.744 212.104 23.062 48.378 86.717
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
表8 TP53INP2通过Wnt/β-catenin影响细胞的侵袭转移（ ± s）
分组 实验次数 细胞迁移数（个） 细胞侵袭数（个） TP53INP2 β-catenin E-cadherin N-cadherin vimentin
对照 3 146.34±13.35 153.67±11.43 1.00±0.11 1.00±0.05 1.00±0.08 1.00±0.07 1.00±0.06
OE-TP53INP2 3 617.33±12.25a 706.56±14.72a 10.25±0.13a 4.12±0.14a 0.23±0.07a 2.45±0.06a 2.34±0.05a
OE-TP53INP2+ XAV-939 3 131.00±21.33b 143.33±17.84b 10.86±0.11 2.46±0.07b 2.12±0.08b 0.47±0.05b 0.52±0.06b
F值   182.229 186.613 152.734 112.124 124.162 138.354 184.627
P值   < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
1
宣雯霞，郭泰，王伏生. 乳腺癌的治疗进展[J]. 中国药物与临床, 2015, 15(2):203-205.
2
曾佳佳，杨润祥，刘蓉. 乳腺癌的靶向治疗研究进展[J]. 中国生化药物杂志, 2016, 36(1):7-11.
3
林潇，胡倩，姚和瑞. 转移性乳腺癌的化疗策略[J]. 中华临床医师杂志(电子版), 2015, 9(6):966-971.
4
戴睿，林萍，宋精玲, 等. miR-541-3p靶向SPOCD1基因通过Wnt/β-catenin信号通路抑制乳腺癌细胞增殖、迁移和侵袭[J]. 中国免疫学杂志, 2021, 37(6):694-699.
5
廖壮文，梁采宇，陈灿伟, 等. 白鲜碱通过Wnt/β-catenin信号通路抑制前列腺癌骨转移PC-3细胞的作用[J]. 实用医学杂志, 2021, 37(3):298-303.
6
张若，张鸢. lncRNA BRE-AS1调控Wnt/β-catenin信号通路影响宫颈癌SiHa细胞增殖、侵袭和凋亡的实验研究[J]. 中国免疫学杂志, 2021, 37(5):577-581, 586.
7
赵越，冯菲，王军, 等. 幽门螺杆菌通过Wnt/β-catenin信号通路对胃癌细胞侵袭及血管新生因子的作用研究[J]. 中国现代医学杂志, 2021, 31(13):5-10.
8
Xu Y, Wan W. The bifunctional role of TP53INP2 in transcription and autophagy[J]. Autophagy, 2020, 16(7):1341-1343.
9
You Z, Xu Y, Wan W, et al. TP53INP2contributes to autophagosome formation by promoting LC3-ATG7 interaction[J]. Autophagy, 2019, 15(8):1309-1321
10
Tie J, Pan Y, Zhao L, et al. MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor[J]. PLoS Genet, 2010, 6(3):e1000879. doi: 10.1371/journal.pgen.1000879.
11
Chu YW, Yang PC, Yang SC, et al. Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cellline[J]. Am J Respir Cell Mol Biol, 1997, 17(3):353-360.
12
Wang CC, Tsai MF, Dai TH, et al. Synergistic activation of the tumor suppressor, HLJ1, by the transcription factors YY1 and activator protein1[J]. Cancer Res, 2007, 67(10):4816-4826.
13
Tseng RC, Lin RK, Wen CK, et al. Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type beta-catenin nuclear accumulation in lung tumorigenesis[J]. Oncogene, 2008, 27(32):4488-4496.
14
Chang DK, Lin CT, Wu CH, et al. A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer[J]. PLOS ONE, 2009, 4(1):e4171. doi: 10.1371/journal.pone.0004171.
15
Torng PL, Lee YC, Huang CY, et al. Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma[J]. Oncogene, 2008, 27(15):2137-2147.
16
Yu SL, Chen HY, Chang GC, et al. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell, 2008, 13(1): 48-57.
17
Sala D, Ivanova S, Plana N, et al. Autophagy-regulating TP53INP2 mediates muscle wasting and is repressed in diabetes[J]. J Clin Invest, 2014, 124(5):1914-1927.
18
Liu X, Klionsky DJ. TP53INP2/DOR protein chaperones deacetylated nuclear LC3 to the cytoplasm to promote macroautophagy[J]. Autophagy, 2015, 11(9):1441-1442.
19
Sancho A, Duran J, García-España A, et al. DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual regulators of autophagy and transcription[J]. PLOS ONE, 2012, 7(3):e34034. doi: 10.1371/journal.pone.0034034.
20
Yin L, Gao Y, Zhang X, et al. Niclosamide sensitizes triplenegative breast cancer cells to ionizing radiation in association with the inhibition of Wnt/β-catenin signaling[J]. Oncotarget, 2016, 7(27):42126-42138.
21
Zou Y, Lin X, Bu J, et al. Timeless-stimulated miR-5188-FOXO1/β-catenin-c-Jun feedback loop promotes stemness via ubiquitination of β-catenin in breast cancer[J]. Mol Ther, 2020, 8(1):313-327
22
Lalefar NR, Witkowski A, Simonsen JB, et al. Wnt3a nanodisks promote ex vivo expansion bof hematopoietic stem and progenitor cells[J]. J Nanobiotechnology, 2016, 14(1) :66. doi: 10.1186/s12951-016-0218-5.
23
Romero M, Sabaté-Pérez A, Francis VA, et al. TP53INP2 regulates adiposity by activating β-catenin through autophagy-dependent sequestration of GSK3β[J]. Nat Cell Biol, 2018, 20(4):443-454.
24
Xu Y, Wan W, Shou X, et al. TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters[J]. Autophagy, 2016, 12(7):1118-1128.
25
Bai H, Li H, Li W, et al. The PI3K/AKT/mTOR pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines[J]. Oncotarget, 2015, 6(28):25520-25532.
[1] 孙帼, 谢迎东, 徐超丽, 杨斌. 超声联合临床特征的列线图模型预测甲状腺乳头状癌淋巴结转移的价值[J]. 中华医学超声杂志（电子版）, 2023, 20(07): 734-742.
[2] 康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[3] 江艺, 张小进, 沈佳佳. 胆囊癌伴肝多发转移手术治疗（腹腔镜下胆囊癌切除+淋巴结清扫+肝Ⅴ、Ⅵ、Ⅶ段切除）[J]. 中华普通外科学文献(电子版), 2023, 17(06): 412-412.
[4] 李雄雄, 周灿, 徐婷, 任予, 尚进. 初诊导管原位癌伴微浸润腋窝淋巴结转移率的Meta分析[J]. 中华普通外科学文献(电子版), 2023, 17(06): 466-474.
[5] 唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[6] 袁育韬, 邢金琳, 谢克飞, 殷凯. CT征象及BRAFV600E基因突变与甲状腺乳头状癌中央区淋巴结转移的相关性[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 611-614.
[7] 晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[8] 徐成, 王璐璐, 王少华. 洗脱液甲状腺球蛋白在甲状腺乳头状癌转移淋巴结中的应用[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 701-704.
[9] 肖体先, 刘骞, 宋京海. 乳房外Paget病脾转移一例报告[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 717-719.
[10] 杨红杰, 张智春, 孙轶. 直肠癌淋巴结转移诊断研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 512-518.
[11] 黄怡诚, 陆晨, 孙司正, 喻春钊. 肝特异性转录因子FOXA2在人结直肠癌肝转移阶梯模型中的表达变化及其意义[J]. 中华结直肠疾病电子杂志, 2023, 12(05): 396-403.
[12] 刘祺, 张凯, 李建男, 刘铜军. 结直肠癌肝转移生物治疗的现状及进展[J]. 中华结直肠疾病电子杂志, 2023, 12(05): 415-419.
[13] 范博洋, 王宁, 张骞, 王贵玉. 结直肠癌转移调控的环状RNA分子机制研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(05): 426-430.
[14] 王小红, 钱晶, 翁文俊, 周国雄, 朱顺星, 祁小鸣, 刘春, 王萍, 沈伟, 程睿智, 秦璟灏. 巯基丙酮酸硫基转移酶调控核因子κB信号介导自噬对重症急性胰腺炎大鼠的影响及机制[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 422-426.
[15] 孔凡彪, 杨建荣. 肝脏基础疾病与结直肠癌肝转移之间关系的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(07): 818-822.
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