Citation: | XU Hexi, SONG Hongqi, LIU Dianwen, LIU Shiju, YANG Huiju. Effect of silencing E26 transformation-specific sequence 4 on proliferation and migration of colon cancer cells by inhibiting nuclear factor-κB signaling pathway[J]. Journal of Clinical Medicine in Practice, 2025, 29(2): 38-41,47. DOI: 10.7619/jcmp.20243267 |
To investigate the mechanism of E26 transformation-specific sequence 4 (ETV4) affecting the proliferation and migration of colon cancer cells through the nuclear factor-κB (NF-κB) signaling pathway.
The expression level of ETV4 in normal colon tissues and cancer tissues was analyzed by the user-friendly interactive cancer transcriptome data analysis resource (UALCAN) database. Reverse transcription quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression level of ETV4 in normal intestinal epithelial cells and colon cancer cell lines. After silencing ETV4 in SW480 cells, qRT-PCR and Western blot were performed to detect the expression of ETV4 to assess transfection efficiency; colony formation and Transwell assays were conducted to explore the effects of ETV4 silencing on the proliferation and migration of colon cancer cells; the Western blot was used to detect the effects of ETV4 silencing on the protein expression of protein 65 (p65) and phosphorylated protein 65 (p-p65) in the NF-κB pathway.
The UALCAN database analysis revealed high expression of ETV4 in colon cancer tissues. The qRT-PCR and Western blot showed that ETV4 expression was significantly higher in the colon cancer cell lines SW480, Lovo, Caco-2, and SW620 than in normal intestinal epithelial cells HIEC-6, with the highest expression in SW480 cells (P < 0.001). Colony formation and Transwell assay results indicated that silencing ETV4 significantly inhibited the proliferation and migration of colon cancer SW480 cells (P < 0.001). Western blot results showed that silencing ETV4 significantly inhibited the expression of p-p65 protein in the cells (P < 0.001).
Silencing ETV4 may inhibit the activation of the NF-κB signaling pathway, thereby inhibiting the proliferation and migration of colon cancer cells.
[1] |
SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2022 [J]. CA: a cancer journal for clinicians, 2022, 72(1): 7-33. doi: 10.3322/caac.21708
|
[2] |
DE NES L C F, VAN DER HEIJDEN J A G, VERSTEGEN M G, et al. Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer[J]. Eur J Surg Oncol, 2022, 48(5): 1144-1152. doi: 10.1016/j.ejso.2021.11.004
|
[3] |
LUO Y, YAO Q. Circ_0085315 promotes cell proliferation, invasion, and migration in colon cancer through miR-1200/MAP3K1 signaling pathway[J]. Cell Cycle, 2022, 21(11): 1194-1211. doi: 10.1080/15384101.2022.2044137
|
[4] |
KOLB J M, MOLMENTI C L, PATEL S G, et al. Increased risk of colorectal cancer tied to advanced colorectal polyps: an untapped opportunity to screen first-degree relatives and decrease cancer burden[J]. Am J Gastroenterol, 2020, 115(7): 980-988. doi: 10.14309/ajg.0000000000000639
|
[5] |
BENZ S R, FEDER I S, VOLLMER S, et al. Complete mesocolic excision for right colonic cancer: prospective multicentre study[J]. Br J Surg, 2022, 110(1): 98-105. doi: 10.1093/bjs/znac379
|
[6] |
XIE M, LIN Z Y, JI X Y, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2[J]. J Hepatol, 2023, 79(1): 109-125. doi: 10.1016/j.jhep.2023.02.036
|
[7] |
QI D D, LU M, XU P F, et al. Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-α signaling[J]. Cancer Commun, 2023, 43(12): 1354-1372. doi: 10.1002/cac2.12482
|
[8] |
GAO X L, JIANG M Z, CHU Y, et al. ETV4 promotes pancreatic ductal adenocarcinoma metastasis through activation of the CXCL13/CXCR5 signaling axis[J]. Cancer Lett, 2022, 524: 42-56. doi: 10.1016/j.canlet.2021.09.026
|
[9] |
CAI L S, CHEN Q X, FANG S Y, et al. ETV4 promotes the progression of gastric cancer through regulating KDM5D[J]. Eur Rev Med Pharmacol Sci, 2020, 24(5): 2442-2451.
|
[10] |
YAO D, BAO Z M, QIAN X, et al. ETV4 transcriptionally activates HES1 and promotes Stat3 phosphorylation to promote malignant behaviors of colon adenocarcinoma[J]. Cell Biol Int, 2021, 45(10): 2129-2139. doi: 10.1002/cbin.11669
|
[11] |
MOSAAD H, AHMED M M, ELAIDY M M, et al. Down-regulated MiRNA 29-b as a diagnostic marker in colorectal cancer and its correlation with ETV4 and Cyclin D1 immunohistochemical expression[J]. Cancer Biomark, 2023, 37(3): 179-189. doi: 10.3233/CBM-220349
|
[12] |
ZHANG W L, HUANG Z C, XIAO Z G, et al. NF-κB downstream miR-1262 disturbs colon cancer cell malignant behaviors by targeting FGFR1[J]. Acta Biochim Biophys Sin, 2023, 55(11): 1819-1832. doi: 10.3724/abbs.2023235
|
[13] |
SUN G, ZHENG C, DENG Z, et al. TRAF5 promotes the occurrence and development of colon cancer via the activation of PI3K/AKT/NF-κB signaling pathways[J]. J Biol Regul Homeost Agents, 2020, 34(4): 1257-1268.
|
[14] |
BENSON A B, VENOOK A P, AL-HAWARY M M, et al. Colon cancer, version 2.202 1, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(3): 329-359. doi: 10.6004/jnccn.2021.0012
|
[15] |
SIEGEL REBECCA L, MILLER KIMBERLY D, ANN G S, et al. Colorectal cancer statistics, 2020[J]. CA a Cancer J Clin, 2020, 70(3): 145-164. doi: 10.3322/caac.21601
|
[16] |
AL-SARAIREH Y M, ALSHAMMARI F O F O, YOUSSEF A M M, et al. Cytochrome 4Z1 expression is associated with poor prognosis in colon cancer patients[J]. Onco Targets Ther, 2021, 14: 5249-5260. doi: 10.2147/OTT.S332037
|
[17] |
SIEGEL R, WAGLE N S, CERCEK A, et al. Colorectal cancer statistics, 2023[J]. CA A Cancer J Clin, 2023, 73: 233-254. doi: 10.3322/caac.21772
|
[18] |
WANG H, DAI Y Y, WANG F X. ETV4-mediated transcriptional activation of SLC12A5 exacerbates ferroptosis resistance and glucose metabolism reprogramming in breast cancer cells[J]. Mol Med Rep, 2024, 30(6): 217. doi: 10.3892/mmr.2024.13341
|
[19] |
ELUARD B, THIEBLEMONT C, BAUD V. NF-κB in the new era of cancer therapy[J]. Trends Cancer, 2020, 6(8): 677-687. doi: 10.1016/j.trecan.2020.04.003
|
[20] |
WENG G X, LING T, HOU W, et al. Mitochondrial DUT-M potentiates RLR-mediated antiviral signaling by enhancing VISA and TRAF2 association[J]. Mol Immunol, 2021, 132: 117-125. doi: 10.1016/j.molimm.2021.01.023
|
[21] |
DIMITRAKOPOULOS F D, KOTTOROU A E, KALOFONOU M, et al. The fire within: NF-κB involvement in non-small cell lung cancer[J]. Cancer Res, 2020, 80(19): 4025-4036. doi: 10.1158/0008-5472.CAN-19-3578
|
[22] |
REN C E, HAN X, LU C, et al. Ubiquitination of NF-κB p65 by FBXW2 suppresses breast cancer stemness, tumorigenesis, and paclitaxel resistance[J]. Cell Death Differ, 2022, 29(2): 381-392. doi: 10.1038/s41418-021-00862-4
|
[23] |
DU F, QI X, ZHANG A T, et al. MRTF-A-NF-κB/p65 axis-mediated PDL1 transcription and expression contributes to immune evasion of non-small-cell lung cancer via TGF-Β[J]. Exp Mol Med, 2021, 53(9): 1366-1378. doi: 10.1038/s12276-021-00670-3
|