The Journal of Practical Medicine >
Expression of LMNB1 in ovarian cancer and its effect on biological behavior of ovarian cancer cells
Received date: 2023-05-03
Online published: 2023-09-26
Objective To investigate the expression of lamin B1（LMNB1） in ovarian cancer and its effect on the proliferation， migration and invasion of ovarian cancer cells and mechanism. Methods Expression of LMNB1 in ovarian cancer tissues and normal ovarian tissues was analyzed by TCGA database and GEO database； Kaplan-Meier plotter was used to analyze the effect of LMNB1 mRNA expression on the prognosis of patients with ovarian cancer. Sixty-eight ovarian cancer specimens and twenty-seven normal ovarian tissues were selected. The level of LMNB1 was detected in ovarian cancer tissues and normal tissues by immunohistochemistry， and the relationship between LMNB1 and clinicopathological features was analysed. LMNB1-knockdowned SKOV3 ovarian cancer cell lines were constructed， then the effects of down-expression of LMNB1 on proliferation， migration， and invasion of ovarian cancer cells were detected by CCK-8， colony formation assay， scratch wound healing assay， transwell assay and Edu assay. The expression of MMP2， MMP9， TIMP1 were detected by Western blot after the LMNB1 expression level was knockdowned. Gene Ontology （GO） and Kyoto Encyelopedia of Gene and Genomes（KEGG）were used to enrich the biological functions and signaling pathways of LMNB1 and related proteins. Results The expression of LMNB1 gene in human ovarian cancer tissues was significantly higher than that in normal ovarian tissues（P < 0.05）. Patients with high LMNB1 expression had poorer overall survival（P < 0.05）. Immunohistochemistry show that the expression level of LMNB1 was significantly upregulated in ovarian cancer tissues（P < 0.05）， and was correlated with pathological differentiation and Pathological stage. Silencing LMNB1 expression in SKOV3 cells significantly inhibited its proliferation， migration and invasion ability（P < 0.05）. LMNB1 and its co-expressed genes are mainly involved in PI3K-AKT pathway， P53 signaling pathway， cell cycle signaling pathway and cell apoptosis pathway. Conclusion The expression of LMNB1 in ovarian cancer tissues was significantly higher than in normal tissues， and strengthened the proliferation，invasion and migration ability of ovarian cancer cells. The mechanism of LMNB1 in ovarian cancer may be to regulate the activities of PI3K-AKT pathway， P53 signaling pathway， cell cycle signaling pathway and cell apoptosis pathway.
Key words： LMNB1; ovarian cancer; invasion; migration
Jianxiang CHENG , Wensheng DU , Min WEI , Guanghui. WANG . Expression of LMNB1 in ovarian cancer and its effect on biological behavior of ovarian cancer cells[J]. The Journal of Practical Medicine, 2023 , 39(16) : 2077 -2084 . DOI: 10.3969/j.issn.1006-5725.2023.16.011
| 1 | ORTIZ M， WABEL E， MITCHELL K， et al. Mechanisms of chemotherapy resistance in ovarian cancer［J］. Cancer Drug Resist，2022， 5（2）：304-316. |
| 2 | 李馨， 张瑜， 倪婷婷， 等. 泛素结合酶E2T基因干扰影响人卵巢癌细胞株SKOV3增殖的作用与机制［J］. 实用医学杂志. 2022， 38（10）：1198-1202，1207. |
| 3 | VERGOTE I， GONZALEZ-MARTIN A， LORUSSO D， et al. Clinical research in ovarian cancer： consensus recommendations from the Gynecologic Cancer InterGroup［J］. Lancet Oncol，2022， 23（8）：e374-e384. |
| 4 | ZHANG R， SIU M K Y， NGAN H Y S， et al. Molecular Biomarkers for the Early Detection of Ovarian Cancer［J］. Int J Mol Sci，2022， 23 （19）：12041. |
| 5 | CRISTOFOLI F， MOSS T， MOORE H W， et al. De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity［J］. Am J Hum Genet，2020， 107（4）：753-762. |
| 6 | BRADY G F， KWAN R， BRAGAZZI CUNHA J， et al. Lamins and Lamin-Associated Proteins in Gastrointestinal Health and Disease［J］. Gastroenterology，2018， 154（6）：1602-1619.e1. |
| 7 | TANG D， LUO H， XIE A， et al. Silencing LMNB1 Contributes to the Suppression of Lung Adenocarcinoma Development［J］. Cancer Manag Res，2021， 13： 2633-2642. |
| 8 | 王瑞官，陈思，孙志佳， 等. 核纤层蛋白B1通过影响端粒酶活性调控肝癌细胞生长［J］. 生物工程学报，2023， 39（4）：1609-1620. |
| 9 | HONG J H， LIANG S T， WANG A S， et al. LMNB1， a potential marker for early prostate cancer progression［J］. Am J Cancer Res，2022， 12， （7）：3390-3404. |
| 10 | YANG Z， SUN Q， GUO J， et al. GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells［J］. Autophagy，2019， 15 （4）：668-685. |
| 11 | YANG Y， GAO L， CHEN J， et al. Lamin B1 is a potential therapeutic target and prognostic biomarker for hepatocellular carcinoma［J］. Bioengineered，2022， 13（4）：9211-9231. |
| 12 | AN Y， YANG Q. Tumor-associated macrophage-targeted therapeutics in ovarian cancer［J］. Int J Cancer，2021， 149（1）：21-30. |
| 13 | HUO X， YAO L， HAN X， et al. Hysterectomy and risk of ovarian cancer： a systematic review and meta-analysis［J］. Arch Gynecol Obstet，2019， 299（3）：599-607. |
| 14 | IRIANTO J， PFEIFER C R， IVANOVSKA I L， et al. Nuclear lamins in cancer［J］. Cell Mol Bioeng， 2016， 9 （2）：258-267. |
| 15 | 邓海孝， 俞泽元， 康继贺，等. 核纤层蛋白家族在恶性肿瘤中的研究进展［J］. 中南大学学报医学版，2020， 45（12）：1490-1498. |
| 16 | PATIL S， SENGUPTA K. Role of A- and B-type lamins in nuclear structure-function relationships［J］. Biol Cell，2021， 113（7）：295-310. |
| 17 | FINNSSON J， LUBBERINK M， SAVITCHEVA I， et al. Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy［J］. Acta Neurol Scand，2019， 139（2）：135-142. |
| 18 | CHEN N Y， YANG Y， WESTON T A， et al. An absence of lamin B1 in migrating neurons causes nuclear membrane ruptures and cell death［J］. Proc Natl Acad Sci U S A，2019， 116 （51）：25870-25879. |
| 19 | 宋章兴， 崔应东， 赵华. LMNB1对前列腺癌患者的临床预后作用［J］. 现代泌尿生殖肿瘤杂志，2017， 9（6）：343-346. |
| 20 | AUGOFF K， HRYNIEWICZ-JANKOWSKA A， TABOLA R， et al. MMP9： A Tough Target for Targeted Therapy for Cancer［J］. Cancers （Basel），2022， 14（7）：1847. |
| 21 | 郝庆刚， 孙凤桂， 严程浩，等. MT1-MMP在肿瘤转移中的研究进展［J］. 遗传，2022， 44 （9）：745-755. |
/
| 〈 |
|
〉 |