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Archive > Volume 31 Issue 2 > 2024,31(2):161-168. DOI:10.3872/j.issn.1007-385X.2024.02.007 Prev Next
Clinical Research
LINC00958 promotes the malignant biological behaviors of cervical cancer cells and lymph node metastasis in mouse models by upregulating VEGF-C expression
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Abstract:
Objective: To investigate the role of LINC00958/vascular endothelial growth factor C (VEGF-C) signaling pathway in lymphovascular formation and lymphatic metastasis in cervical cancer. Methods: 42 samples of cervical cancer tissues and corresponding adjacent tissues were collected from patients who underwent surgery at Henan Provincial People's Hospital between September 2020 and September 2022. The expressions of LINC00958 in cervical cancer specimens and cervical cancer cells (Hela, C33A, SiHa, Caski) were examined by qPCR. Caski cells were transfected with LINC00958 overexpression vector (LINC00958 group) or vehicle control (CMV group), and SiHa cells were transfected with shRNA sequences of knocked-down LINC00958 (shLINC00958 group) and VEGF-C (shVEGF-C group), or negative control shRNA (shNC group). The effects of overexpressed or knocked-down LINC00958 on the proliferation, migration and invasion of cervical cancer cells were detected by CCK-8 method and Transwell assay, respectively. The effect of the culture supernatant of transfected cells on the lymphovascular formation capacity of human lymphatic endothelial cells (HLEC) was observed. A mouse popliteal lymph node metastasis model was established to investigate the effects of overexpressed LINC00958 or simultaneous knockdown of VEGF-C on cervical cancer lymph node metastasis. Results: LINC00958 was highly expressed in cervical cancer tissues (P<0.001), and high levels of LINC00958 were associated with large tumors, advanced tumor grade, depth of invasion, and lymphatic metastasis (P<0.05 or P<0.01). Compared with that in the normal human cervical epithelial cells ende1617, the level of LINC00958 in cervical cancer cells was significantly increased (P<0.01 or P<0.001). The proliferation, migration and invasion abilities of SiHa cells in the shLINC00958 group and the HLEC lymph vessel pro-formation ability of the culture supernatant were significantly lower than those in the shNC group (P<0.05, P<0.01 or P<0.001), and the proliferation, migration and invasion abilities of Caski cells in the LINC00958 group and the HLEC lymph vessel pro-formation ability of the culture supernatant were significantly higher than those in the CMV group (P<0.05, P<0.01 or P<0.001). RNA pull-down and RNA immunoprecipitation assays showed that LINC00958 in cervical cancer cells could specifically bind to VEGF-C. The proliferation, migration and invasion abilities of Caski cells in the LINC00958+shVEGF-C group and the lymph vessel pro-formation ability of the culture supernatant were significantly lower than those in the LINC00958 group (P<0.01 or P<0.001). In the mouse popliteal lymph node metastasis model, the volume of popliteal lymph nodes in the LINC00958+shVEGF-C group and the proportion of VEGF-C protein, N-cadherin protein and LYVE-1 positive cells were significantly lower than those in the LINC00958 group (all P<0.001). Conclusion: LINC00958 directly interacts with VEGF-C protein to enhance the proliferation and invasion abilities and lymph vessel formation ability of cervical cancer cells, and promote lymph node metastasis in the mouse popliteal lymph node metastasis model.
Keywords:
LINC00958 ; vascular endothelial growth factor C (VEGF-C) ; cervical cancer ; Caski cell ; SiHa cell ; lymphovascular formation ; lymph node metastasis
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靖爽,和晓利,井佳雨,王悦. LINC00958 通过上调VEGF-C 表达促进宫颈癌细胞的恶性生物学行为及小鼠模型的淋巴结转移[J].中国肿瘤生物治疗杂志,2024,31(2):161~168
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History
Manuscript received: August 27,2023
Manuscript revised: January 03,2024
Online Published: April 09,2024