Journal of Surgery Concepts & Practice››2024,Vol. 29››Issue (02): 161-169.doi:10.16139/j.1007-9610.2024.02.12
• Original article •Previous ArticlesNext Articles
WU Xiongyan1, LI Zhen2, YU Zhenjia1, SU liping1(
)
Received:2023-07-05Online:2024-03-25Published:2024-07-01Contact:SU liping E-mail:suliping@shsmu.edu.cnCLC Number:
WU Xiongyan, LI Zhen, YU Zhenjia, SU liping. Role and possible mechanism of pseudogeneFMO6Pin inhibiting invasion and metastasis of gastric cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(02): 161-169.
Fig 1
The expression of FMO6P decreased in gastric cancer tissues A: Waterfall plot showing fold changes of FMO6P in gastric cancer tissues and adjacent non-tumor tissues (n=100); B: Relative expression levels of FMO6P in gastric cancer tissues compared to adjacent non-tumor tissues. *P<0.05.
Tab 1
Correlation between mRNA expression level of FMO6P and clinical pathology in gastric cancer
| Expression ofFMO6P | χ2/Z/tvalue | Pvalue | ||
|---|---|---|---|---|
| High(n=11) | Low(n=69) | |||
| Gender | 0.695 | 0.404 | ||
| Male | 9 | 48 | ||
| Female | 2 | 21 | ||
| Age | 0.155 | 0.693 | ||
| > 60 years | 7 | 48 | ||
| ≤ 60 years | 4 | 21 | ||
| Tumor diameter (cm) | 8.449 | 0.003 | ||
| > 5 | 5 | 58 | ||
| ≤ 5 | 6 | 11 | ||
| Pathological T stage | 9.323 | 0.002 | ||
| T1, T2 | 8 | 8 | ||
| T3, T4 | 11 | 61 | ||
| Pathological N stage | 1.382 | 0.239 | ||
| - | 2 | 25 | ||
| + | 9 | 44 | ||
| Metastasis | 0.949 | 0.330 | ||
| - | 9 | 63 | ||
| + | 2 | 6 | ||
| TNM stage | 4.071 | 0.043 6 | ||
| Ⅰ+Ⅱ | 1 | 28 | ||
| Ⅲ+Ⅳ | 10 | 41 | ||
Fig 2
Construction of FMO6P overexpressing and knocking down stable transfected gastric cancer cells The expression level of FMO6P mRNA was detected in knockdown or overexpression of FMO6P in gastric cancer cells MGC-803 or HGC-27 stable transfected cell lines, n=3, *P<0.05, **P<0.01.
Fig 3
FMO6P inhibited the invasion and migration ability of gastric cancer cells A: Overexpression of FMO6P inhibited the migration ability of gastric cancer cells (200 x); B: Knocking down FMO6P promoted the migration ability of gastric cancer cells (200 x); C: Overexpression of FMO6P inhibited the invasive ability of gastric cancer cells (200 x); D: Knocking down FMO6P promoted the invasive ability of gastric cancer cells (200 x); E: Transwell invasion and migration cell count (* P<0.05, * * P<0.01, * * * P<0.001)
Fig 4
FMO6P inhibited EMT in gastric cancer cells A: The expression levels of EMT markers after overexpression or knockdown of FMO6P in gastric cancer cells; B: Statistical analysis of grayscale values of protein bands in Fig 4A (*P<0.05, **P<0.01, ***P<0.001).
Fig 5
FMO6P inhibited the subcutaneous tumorigenesis ability, and intraperitoneal implantation and dissemination ability of gastric cancer cells in nude mice A: Growth curve of FMO6P-overexpressing gastric cancer cells in nude mice subcutaneously; B: The tumor size of FMO6P-overexpressing gastric cancer cells formed after 30 days of subcutaneous inoculation in nude mice; C: Statistical analysis of the number of peritoneal metastatic nodules formed after 4 weeks of intraperitoneal inoculation of FMO6P-overexpressing gastric cancer cells in nude mice; D: Peritoneal metastatic nodules formed after 4 weeks of intraperitoneal inoculation of FMO6P-overexpressing gastric cancer cells in nude mice.
Fig 6
FMO6P inhibited the activation of AKT/mTOR signaling pathway in gastric cancer cells A: The activation levels of AKT and mTOR after overexpression or knockdown of FMO6P in gastric cancer cells; B: Statistical analysis of grayscale values of protein bands in Fig6A (*P<0.05, **P<0.01, ***P<0.001).
| [1] | YANG L, ZHENG R S, WANG N, et al. Incidence and mortality of stomach cancer in China 2014[J].Chin J Cancer Res,2018,30(3):291-298. |
| [2] | MIGUEL V, LAMAS S, ESPINOSA-DIEZ C. Role of non-coding-RNAs in response to environmental stressors and consequences on human health[J].Redox Biol,2020,37:101580. |
| [3] | XIAO-JIE L, AI-MEI G, LI-JUAN J, et al. Pseudogene in cancer:real functions and promising signature[J].J Med Genet,2015,52(1):17-24. |
| [4] | MA H W, MA T S, CHEN M, et al. The pseudogene-derived long non-coding RNA SFTA1P suppresses cell proliferation,migration,and invasion in gastric cancer[J].Biosci Rep,2018,38(2):BSR20171193. |
| [5] | LI D D, SHE J J, HU X H, et al. The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA-RNA interactions and drives gastric cancer metastasisviamiR-138-5p/ITGA2 axis[J].Oncogene,2021,40(35):5403-5415. |
| [6] | GUO Y M, WANG Y M, MA Y L, et al. Upregulation of lncRNA SUMO1P3 promotes proliferation, invasion and drug resistance in gastric cancer through interacting with the CNBP protein[J].RSC Adv,2020,10(10):6006-6016. doi:10.1039/c9ra09497kpmid:35497433 |
| [7] | XU Y C, YU Y, WEI C C, et al. Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and invasion by regulating LATS1 and beta-catenin in gastric cancer[J].J Exp Clin Cancer Res,2018,37(1):13. |
| [8] | HERNANDEZ D, JANMOHAMED A, CHANDAN P, et al. Organization and evolution of the flavin-containing monooxygenase genes of human and mouse:identification of novel gene and pseudogene clusters[J].Pharmacogene-tics,2004,14(2):117-130. |
| [9] | FIORENTINI F, GEIER M, BINDA C, et al. Biocatalytic characterization of human FMO5: unearthing baeyer-villiger reactions in humans[J].ACS Chem Biol,2016,11(4):1039-1048. doi:10.1021/acschembio.5b01016pmid:26771671 |
| [10] | LI H, YU B Q, LI J F, et al. Characterization of differentially expressed genes involved in pathways associated with gastric cancer[J].PLoS One,2015,10(4):e0125013. |
| [11] | PASTUSHENKO I, BLANPAIN C. EMT transition states during tumor progression and metastasis[J].Trends Cell Biol,2019,29(3):212-226. doi:S0962-8924(18)30201-0pmid:30594349 |
| [12] | SAITOH M. Involvement of partial EMT in cancer progression[J].J Biochem,2018,164(4):257-264. doi:10.1093/jb/mvy047pmid:29726955 |
| [13] | SINGH M, YELLE N, VENUGOPAL C, et al. EMT:mechanisms and therapeutic implications[J].Pharmacol Ther,2018,182:80-94. |
| [14] | FATTAHI S, AMJADI-MOHEB F, TABARIPOUR R, et al. PI3K/AKT/mTOR signaling in gastric cancer: epigenetics and beyond[J].Life Sci,2020,262:118513. |
| [15] | WANG X J, LI X D, LIN F K, et al. The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis[J].J Exp Clin Cancer Res,2021,40(1):151. doi:10.1186/s13046-021-01957-zpmid:33933142 |
| [16] | ZHANG L M, WANG P, LIU X M, et al. LncRNA SUMO1P3 drives colon cancer growth, metastasis and angiogenesis[J].Am J Transl Res,2017,9(12):5461-5472. |
| [17] | WANG X H, ZHANG L H, LIANG Q Y, et al. DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance[J].Oncogenesis,2022,11(1):66. doi:10.1038/s41389-022-00441-3pmid:36307394 |
| [18] | BAKIR B, CHIARELLA A M, PITARRESI J R, et al. EMT,MET,plasticity,and tumor metastasis[J].Trends Cell Biol,2020,30(10):764-776. |
| [19] | BAJ J, KORONA-GŁOWNIAK I, FORMA I, et al. Mechanisms of the epithelial-mesenchymal transition and tumor microenvironment inhelicobacter pylori-induced gastric cancer[J].Cells,2020,9(4):1055. |
| [20] | NOOROLYAI S, SHAJARI N, BAGHBANI E, et al. The relation between PI3K/AKT signalling pathway and cancer[J].Gene,2019,698:120-128. doi:S0378-1119(19)30217-3pmid:30849534 |
| [21] | YANG X, ZHU W. ERBB3 mediates the PI3K/AKT/mTOR pathway to alter the epithelial-mesenchymal transition in cervical cancer and predict immunity filtration outcome[J].Exp Ther Med,2023,25(4):146. |
| [22] | LI H, GUAN B X, LIU S, et al. PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway[J].Cell Death Dis,2023,14(3):188. doi:10.1038/s41419-023-05712-4pmid:36898991 |
| [23] | CHEN H R, ZHANG L F, ZUO M N, et al. Inhibition of apoptosis through AKT-mTOR pathway in ovarian cancer and renal cancer[J].Aging(Albany NY),2023,15(4):1210-1227. |
| [24] | GHAREGHOMI S, ATABAKI V, ABDOLLAHZADEH N, et al. Bioactive PI3-kinase/Akt/mTOR inhibitors in targeted lung cancer therapy[J].Adv Pharm Bull,2023,13(1):24-35. doi:10.34172/apb.2023.003pmid:36721812 |
| [25] | WANG H W, CHEN Y J, YUAN Q Z, et al. HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway[J].Front Oncol,2022,12:1053510. |
| [26] | LI P, ZHANG Z, LV H, et al. Inhibiting the expression of STARD3 induced apoptosisviathe inactivation of PI3K/AKT/mTOR pathway on ER(+) breast cancer[J].Tissue Cell,2022,79:101971. |
| [27] | PETERSON R T, BEAL P A, COMB M J, et al. FKBP12-rapamycin-associated protein (FRAP) autophosphorylates at serine 2481 under translationally repressive conditions[J].J Biol Chem,2000,275(10):7416-7423. doi:10.1074/jbc.275.10.7416pmid:10702316 |
| [28] | NAVÉ B T, OUWENS M, WITHERS D J, et al. Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation[J].Biochem J,1999,344 Pt 2(Pt 2):427-431. |
| [29] | WANG C, YANG Z, XU E, et al. Apolipoprotein C-Ⅱ induces EMT to promote gastric cancer peritoneal metastasisviaPI3K/AKT/mTOR pathway[J].Clin Transl Med,2021,11(8):e522. |
| [30] | WANG J, JIANG C H, LI N, et al. The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSFviaEMT and the PI3K/Akt/mTOR pathway[J].Cell Death Dis,2020,11(8):682. |
| [31] | MA Z, LOU S P, JIANG Z. PHLDA2 regulates EMT and autophagy in colorectal cancerviathe PI3K/AKT signa-ling pathway[J].Aging(Albany NY),2020,12(9):7985-8000. |
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