收稿日期: 2023-08-09
网络出版日期: 2024-06-13
基金资助
安徽省卫生健康科研项目(AHWJ2022b079);安徽省临床重点专科建设项目(2023-25)
TMSB10 promotes gastric cancer proliferation and glycolysis based on activation of AMPK/mTOR signaling pathway
Received date: 2023-08-09
Online published: 2024-06-13
目的 探究胸腺素β10（thymosin β10， TMSB10）在胃癌中的表达及促进胃癌进展的分子机制。 方法 收集蚌埠医学院第二附属医院70例胃癌患者病理切片，免疫组化检测TMSB10在胃腺癌中的表达，并分析其预后影响。为研究作用机制，通过转染技术、CCK8实验、EDU实验、Transwell小室实验，划痕实验，糖酵解实验，蛋白印迹实验，观察TMSB10对胃癌细胞的增殖和糖酵解的影响及机制研究。 结果 临床样本免疫组化显示，TMSB10在胃癌中高表达。同时，TMSB10的表达水平与肿瘤大小（P < 0.05）、TNM分期（P < 0.01）和远处转移具有相关性。在机制研究中，通过体外实验CCK-8、EDU实验、Transwel实验及糖酵解检测实验发现过表达TMSB10后促进胃癌细胞增殖、侵袭、迁移及糖酵解表型，反之亦然。Western blot实验结果显示过表达TMSB10可能通过上调AMPK/mTOR信号通路调节胃癌的发生。 结论 TMSB10通过AMPK/mTOR信号通路促进胃癌细胞增殖、侵袭、迁移及糖酵解过程。
关键词： 胸腺素β10; 糖酵解; 胃癌; AMPK/mTOR信号通路
王畏 , 张新鑫 , 王广辉 , 张杰 , 陈安然 , 贾建光 . TMSB10促进胃癌细胞增殖及糖酵解：基于激活AMPK/mTOR信号通路[J]. 实用医学杂志, 2024 , 40(11) : 1519 -1525 . DOI: 10.3969/j.issn.1006-5725.2024.11.009
Objective To investigate the expression of Thymosinβ10 （TMSB10） in gastric cancer and its molecular mechanism in promoting the progression of gastric cancer. Methods We collected pathological sections of 70 patients with gastric cancer in our hospital， detected expression of TMSB10 in gastric adenocarcinoma by immunohistochemistry， and analyzed its prognostic effect. In order to study the mechanism of action， the effects of TMSB10 on the proliferation and glycolysis of gastric cancer cells and its related mechanism were observed by transfection technique， CCK8 test， EDU assay， Transwell assay， scratch test， glycolysis assay and Western blot. Results Immunohistochemistry showed that TMSB10was highly expressed in gastric cancer， while the expression level of TMSB10 was correlated with tumor size （P = 0.032）， TNM stage （P = 0.002） and distant metastasis. In the mechanism study， we found that overexpression of TMSB10 promoted the proliferation， invasion， migration and glycolytic phenotype of gastric cancer cells through in vitro CCK-8 test， EDU assay， Transwel assay and glycolysis assay， and vice versa. Western blot results showed that overexpression of TMSB10 may regulate the occurrence of gastric cancer through up-regulation of the AMPK/mTOR signaling pathway. Conclusions TMSB10 promotes the proliferation， invasion， migration and glycolysis gastric cancer through the AMPK/mTOR signaling pathway.
Key words： TMSB10; glycolysis; gastric cancer; AMPK/mTOR signaling pathway
| 1 | SIEGEL R L， MILLER K D， WAGLEE N S， et al. Cancer statistics， 2023［J］. CA Cancer J Clin， 2023，73（1）：17-48. doi:10.3322/caac.21763 |
| 2 | SUNG H， FERLAY J， SIEGEL R L， et al. Global Cancer Statistics 2020： GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries［J］. CA Cancer J Clin， 2021，71（3）：209-249. doi:10.3322/caac.21660 |
| 3 | BALAKRISHNAN M， GEORGE R， SHARMA A， et al. Changing Trends in Stomach Cancer Throughout the World［J］. Curr Gastroenterol Rep， 2017，19（8）：36-40. doi:10.1007/s11894-017-0575-8 |
| 4 | YAN Z， YAN Q， SONG Y， et al. TMSB10， a potential prognosis prediction biomarker， promotes the invasion and angiogenesis of gastric cancer［J］. J Gastroenterol Hepatol， 2021，36（11）：3102-3112. doi:10.1111/jgh.15576 |
| 5 | SONG C， SU Z， GUO J. Thymosin β 10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma［J］. Biosci Rep， 2019，39（3）：BSR20182355. doi:10.1042/bsr20182355 |
| 6 | 张萌， 刘旭明， 麦皓尘，等. SLC7A11在KRAS突变胰腺癌中的表达及临床意义［J］. 实用医学杂志， 2022，38（24）：3125-3128. doi:10.3969/j.issn.1006?5725.2022.24.018 |
| 7 | ZHOU Y， CHEN Y， SHI Y， et al. FAM117B promotes gastric cancer growth and drug resistance by targeting the KEAP1/NRF2 signaling pathway［J］. J Clin Invest， 2023，133（3）：1-8. doi:10.1172/jci158705 |
| 8 | LEE M， CHO H J， PARK K S， et al. ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes［J］. Int J Mol Sci， 2022，23（7）：1-9. doi:10.3390/ijms23073709 |
| 9 | CHEN Z， YUAN L， LI X， et al. BMP2 inhibits cell proliferation by downregulating EZH2 in gastric cancer［J］. Cell Cycle， 2022，21（21）：2298-2308. doi:10.1080/15384101.2022.2092819 |
| 10 | LI S， GUO D， SUN Q， et al. MAPK4 silencing in gastric cancer drives liver metastasis by positive feedback between cancer cells and macrophages［J］. Exp Mol Med， 2023，55（2）：457-469. doi:10.1038/s12276-023-00946-w |
| 11 | GUO R， CUI X， LI X， et al. CircMAN1A2 is upregulated by Helicobacter pylori and promotes development of gastric cancer［J］. Cell Death Dis， 2022，13（4）：409-415. doi:10.1038/s41419-022-04811-y |
| 12 | LI Y， LI L， LIU H， et al. CPNE1 silencing inhibits cell proliferation and accelerates apoptosis in human gastric cancer［J］. Eur J Pharm Sci， 2022，177（1）：106278-106289. doi:10.1016/j.ejps.2022.106278 |
| 13 | GENG S， PENG W， WANG X， et al. ARIH2 regulates the proliferation， DNA damage and chemosensitivity of gastric cancer cells by reducing the stability of p21 via ubiquitination［J］. Cell Death Dis， 2022，13（6）：564-578. doi:10.1038/s41419-022-04965-9 |
| 14 | ZHANG G， ZHU Q， YAN X， et al. HECTD3 promotes gastric cancer progression by mediating the polyubiquitination of c-MYC［J］. Cell Death Discov， 2022，8（1）：185-195. doi:10.1038/s41420-022-01001-9 |
| 15 | LI D， WANG Y， DONG C， et al. CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1［J］. Oncogene， 2023，42（2）：83-98. doi:10.1038/s41388-022-02537-x |
| 16 | YAN C， YANG H， SU P， et al. OTUB1 suppresses Hippo signaling via modulating YAP protein in gastric cancer［J］. Oncogene， 2022，41（48）：5186-5198. doi:10.1038/s41388-022-02507-3 |
| 17 | LI J， ZHOU S， LI H， et al. PTEN/AKT upregulation of TMSB10 contributes to lung cancer cell growth and predicts poor survival of the patients［J］. Biosci Biotechnol Biochem， 2021，85（4）：805-813. doi:10.1093/bbb/zbaa113 |
| 18 | WANG C， HE Y， YOU Z， et al. TMSB10 Promotes Progression of Clear Cell Renal Cell Carcinoma via JUN Transcription Regulation［J］. Ann Clin Lab Sci， 2022，52（2）：230-239. |
| 19 | PAN Q， CHENG G， LIU Y， et al. TMSB10 acts as a biomarker and promotes progression of clear cell renal cell carcinoma［J］. Int J Oncol， 2020，56（5）：1101-1114. |
| 20 | XIONG Y， QI Y， PAN Z， et al. Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma［J］. Cancer Cell Int， 2022，22（1）：294-305. doi:10.1186/s12935-022-02698-5 |
| 21 | LEE S H， ZHANG W， CHOI J J， et al. Overexpression of the thymosin beta-10 gene in human ovarian cancer cells disrupts F-actin stress fiber and leads to apoptosis［J］. Oncogene， 2001，20（46）：6700-6706. doi:10.1038/sj.onc.1204683 |
| 22 | SRIBENJA S， SAWANYAWISUTH K， KRAIKLANG R， et al. Suppression of thymosin β10 increases cell migration and metastasis of cholangiocarcinoma［J］. BMC Cancer， 2013，13（1）：430-438. doi:10.1186/1471-2407-13-430 |
| 23 | FANG G， ZHANG P， LIU J， et al. Inhibition of GSK-3β activity suppresses HCC malignant phenotype by inhibiting glycolysis via activating AMPK/mTOR signaling［J］. Cancer Lett， 2019，463（1）：11-26. doi:10.1016/j.canlet.2019.08.003 |
/
| 〈 |
|
〉 |