MiR-99a-5p Constrains Epithelial-Mesenchymal Transition of Cervical Squamous Cell Carcinoma Via Targeting CDC25A/IL6

被引:7
作者
Gu, Ailing [1 ]
Bao, Xudong [1 ]
机构
[1] Wuxi 2 Chinese Med Hosp, Dept Obstet & Gynecol, 390 Xincheng Rd, Wuxi 214026, Jiangsu, Peoples R China
关键词
miR-99a-5p; cervical squamous cell carcinoma (CSCC); CDC25A; Migration; Invasion; Apoptosis; IL-6; PANCREATIC-CANCER; PROLIFERATION; MIGRATION; INTERLEUKIN-6; PHOSPHATASES; INVASION; MICRORNA; GROWTH; ROLES;
D O I
10.1007/s12033-022-00496-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MiR-99a-5p participates in processes and pathogenesis of varying diseases. However, the molecular mechanism of miR-99a-5p in human cervical squamous cell carcinoma (CSCC) remains unclear. Here, we found that miR-99a-5p was lowly expressed in CSCC cells and negatively associated with overall survival. In addition, cellular experiments including CCK8, wound healing, Transwell and flow cytometry assays disclosed that transfection of miR-99a-5p mimic could suppress the cell activity, cell migratory, and invasive abilities, and promote cell apoptosis, thus inhibiting the tumor progression of CSCC cells. Luciferase reporter gene assay indicated that miR-99a-5p targeted 3'-UTR of CDC25A. Also, enforced CDC25A level rescued the impact of miR-99a-5p on CSCC progression. Silencing CDC25A could restrain the mRNA and protein levels of IL-6 in CSCC. CDC25A overexpression or IL-6 treatment could attenuate inhibiting impact of miR-99a-5p overexpression on epithelial-mesenchymal transition (EMT). These findings suggested that miR-99a-5p may play an anti-tumor role in tumor metastasis by targeting CDC25A/IL6 to hamper EMT process, which revealed a novel molecular mechanism in CSCC.
引用
收藏
页码:1234 / 1243
页数:10
相关论文
共 37 条
[1]   Accumulation of cytoplasmic CDC25A in cutaneous squamous cell carcinoma leads to a dependency on CDC25A for cancer cell survival and tumor growth [J].
Al-Matouq, Jenan ;
Holmes, Thomas ;
Hammiller, Brianna ;
Tran, Nicholas ;
Holmes, Matti ;
Freeman, S. Caleb ;
Hansen, Laura A. .
CANCER LETTERS, 2017, 410 :41-49
[2]   Gene of the month: Interleukin 6 (IL-6) [J].
Ataie-Kachoie, Parvin ;
Pourgholami, Mohammad H. ;
Richardson, Des R. ;
Morris, David L. .
JOURNAL OF CLINICAL PATHOLOGY, 2014, 67 (11) :932-937
[3]   CDC25A governs proliferation and differentiation of FLT3-ITD acute myeloid leukemia [J].
Bertoli, Sarah ;
Boutzen, Helena ;
David, Laure ;
Larrue, Clement ;
Vergez, Francois ;
Fernandez-Vidal, Anne ;
Yuan, Lingli ;
Hospital, Marie-Anne ;
Tamburini, Jerome ;
Demur, Cecile ;
Delabesse, Eric ;
Saland, Estelle ;
Sarry, Jean-Emmanuel ;
Galcera, Marie-Odile ;
Mansat-De Mas, Veronique ;
Didier, Christine ;
Dozier, Christine ;
Recher, Christian ;
Manenti, Stephane .
ONCOTARGET, 2015, 6 (35) :38061-38078
[4]   Cdc25A phosphatase: a key cell cycle protein that regulates neuron death in disease and development [J].
Biswas, Subhas Chandra ;
Sanphui, Priyankar ;
Chatterjee, Nandini ;
Kemeny, Stav ;
Greene, Lloyd A. .
CELL DEATH & DISEASE, 2017, 8 :e2692-e2692
[5]   Integrated genomic and molecular characterization of cervical cancer [J].
Burk, Robert D. ;
Chen, Zigui ;
Saller, Charles ;
Tarvin, Katherine ;
Carvalho, Andre L. ;
Scapulatempo-Neto, Cristovam ;
Silveira, Henrique C. ;
Fregnani, Jose H. ;
Creighton, Chad J. ;
Anderson, Matthew L. ;
Castro, Patricia ;
Wang, Sophia S. ;
Yau, Christina ;
Benz, Christopher ;
Robertson, A. Gordon ;
Mungall, Karen ;
Lim, Lynette ;
Bowlby, Reanne ;
Sadeghi, Sara ;
Brooks, Denise ;
Sipahimalani, Payal ;
Mar, Richard ;
Ally, Adrian ;
Clarke, Amanda ;
Mungall, Andrew J. ;
Tam, Angela ;
Lee, Darlene ;
Chuah, Eric ;
Schein, Jacqueline E. ;
Tse, Kane ;
Kasaian, Katayoon ;
Ma, Yussanne ;
Marra, Marco A. ;
Mayo, Michael ;
Balasundaram, Miruna ;
Thiessen, Nina ;
Dhalla, Noreen ;
Carlsen, Rebecca ;
Moore, Richard A. ;
Holt, Robert A. ;
Jones, Steven J. M. ;
Wong, Tina ;
Pantazi, Angeliki ;
Parfenov, Michael ;
Kucherlapati, Raju ;
Hadjipanayis, Angela ;
Seidman, Jonathan ;
Kucherlapati, Melanie ;
Ren, Xiaojia ;
Xu, Andrew W. .
NATURE, 2017, 543 (7645) :378-+
[6]   Silencing CDC25A inhibits the proliferation of liver cancer cells by downregulating IL-6 in vitro and in vivo [J].
Chen, Si ;
Tang, Yanping ;
Yang, Chun ;
Li, Kezhi ;
Huang, Xiaoqing ;
Cao, Ji .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2020, 45 (03) :743-752
[7]   Biological role and clinical value of miR-99a-5p in head and neck squamous cell carcinoma (HNSCC): A bioinformatics-based study [J].
Chen, Yu-ting ;
Yao, Jian-ni ;
Qin, Yu-tao ;
Hu, Kai ;
Wu, Fang ;
Fang, Ye-ying .
FEBS OPEN BIO, 2018, 8 (08) :1280-1298
[8]   Causes and consequences of microRNA dysregulation in cancer [J].
Croce, Carlo M. .
NATURE REVIEWS GENETICS, 2009, 10 (10) :704-714
[9]   MicroRNA-21 is Overexpressed in Pancreatic Cancer and a Potential Predictor of Survival [J].
Dillhoff, Mary ;
Liu, James ;
Frankel, Wendy ;
Croce, Carlo ;
Bloomston, Mark .
JOURNAL OF GASTROINTESTINAL SURGERY, 2008, 12 (12) :2171-2176
[10]   CyclinD-CDK4/6 complexes phosphorylate CDC25A and regulate its stability [J].
Dozier, C. ;
Mazzolini, L. ;
Cenac, C. ;
Froment, C. ;
Burlet-Schiltz, O. ;
Besson, A. ;
Manenti, S. .
ONCOGENE, 2017, 36 (26) :3781-3788