Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Cervical Cancer | Primary research

miR-125a-5p post-transcriptionally suppresses GALNT7 to inhibit proliferation and invasion in cervical cancer cells via the EGFR/PI3K/AKT pathway

Authors: Qinxue Cao, Ning Wang, Lu Ren, Jun Tian, Shaoqin Yang, Hailing Cheng

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

The carcinogenesis and progression of cervical cancer is a complex process in which numerous microRNAs are involved. The purpose of this study is to investigate the role of miR-125a-5p in progression of cervical cancer.

Methods

RT-qPCR was used to detect the expression of miR-125a-5p and GALNT7 in cervical cancer tissues and cell lines. Then, the miR-125a-5p mimic, miR-125a-5p inhibitor, GALNT7 siRNA, or/and pcDNA-GALNT7 were respectively transfected into HeLa and Caski cervical cancer cells, and Cell Counting kit-8 assay, Transwell assay and flow cytometry analysis were respectively used to observe cell proliferation, invasion and apoptosis. Subsequently, luciferase reporter gene assay was employed in confirming the target relationship between miR-125a-5p and GALNT7. MiR-125a-5p mimic or/and pcDNA-GALNT7 were transfected into the cervical cancer cells at the absence of epidermal growth factor (EGF) or not, and the pcDNA-GALNT7 was transfected into the cervical cancer cells at the absence of inhibitors of multiple kinases or not. Furthermore, the effect of miR-125a-5p on tumor growth was also studied using a xenograft model of nude mice.

Results

MiR-125a-5p was down-regulated in both cervical cancer tissues and cell lines and it inhibited cell proliferation and invasion of cervical cancer cells. MiR-125a-5p directly targeted and post-transcriptionally downregulated GALNT7 that was strongly upregulated in cervical cancer tissues and cell lines. Similar to the effect of miR-125a-5p mimic, silencing GALNT7 inhibited proliferation and invasion of cervical cancer cells. In addition, miR-125a-5p overexpression could counteract both GALNT7- and EGF-induced cell proliferation and invasion. GALNT7 promoted cell proliferation and invasion by activating the EGFR/PI3K/AKT kinase pathway, which could be abated by the inhibitors of the kinases. Moreover, the role of miR-125a-5p inhibited tumor formation in cervical cancer by suppressing the expression of GALNT7 in vivo.

Conclusion

In conclusion, miR-125a-5p suppressed cervical cancer progression by post-transcriptionally downregulating GALNT7 and inactivating the EGFR/PI3K/AKT pathway.
Literature
1.
Liang C, Ding J, Yang Y, Deng L, Li X. MicroRNA-433 inhibits cervical cancer progression by directly targeting metadherin to regulate the AKT and β-catenin signalling pathways. Oncol Rep. 2017;38(6):3639–49.PubMed
2.
Zhang J, Yao T, Wang Y, Yu J, Liu Y, Lin Z. Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21. Cancer Biol Ther. 2016;17(1):104–13.PubMedCrossRef
3.
Wei WF, Zhou CF, Wu XG, He LN, Wu LF, Chen XJ, Yan RM, Zhong M, Yu YH, Liang L. MicroRNA-221-3p, a TWIST2 target, promotes cervical cancer metastasis by directly targeting THBS2. Cell Death Dis. 2017;8(12):3220–49.PubMedPubMedCentralCrossRef
4.
Chen G, Huang P, Xie J, Li R. microRNAa-211 suppresses the growth and metastasis of cervical cancer by directly targeting ZEB1. Mol Med Rep. 2017;17(1):1275–82.PubMed
5.
Hua FF, Liu SS, Zhu LH, Wang YH, Liang X, Ma N, Shi HR. MiRNA-338-3p regulates cervical cancer cells proliferation by targeting MACC1 through MAPK signaling pathway. Eur Rev Med Pharmacol Sci. 2017;21(23):5342–52.PubMed
6.
7.
Gao YL, Zhao ZS, Zhang MY, Han LJ, Dong YJ, Xu B. Long non-coding RNA PVT1 facilitates cervical cancer progression via negative regulating of miR-424. Oncol Res. 2017;25(8):1391–8.PubMedCrossRefPubMedCentral
8.
Inui M, Martello GS. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol. 2010;11(4):252–63.PubMedCrossRef
9.
Yiming L, Yang Z, Wubin Q, Minghua D, Chenggang Z. A Lasso regression model for the construction of microRNA-target regulatory networks. Bioinformatics. 2011;27(17):2406–13.CrossRef
10.
Siomi H, Siomi MC. Posttranscriptional regulation of MicroRNA biogenesis in animals. Mol Cell. 2010;38(3):323–32.PubMedCrossRef
11.
Sam GJ, Grocock RJ, Stijn VD, Alex B, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34(suppl 1):140–4.
12.
Zhang Y, Guan DH, Bi RX, Xie J, Yang CH, Jiang YH. Prognostic value of microRNAs in gastric cancer: a meta-analysis. Oncotarget. 2017;8(33):55489–510.PubMedPubMedCentralCrossRef
13.
Zhao Y, Srivastava D. A developmental view of microRNA function. Trends in Biochem Sci. 2007;32(4):189–97.CrossRef
14.
Veerle R, Naar AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012;13(4):239–50.CrossRef
15.
Liang Y, Ye J, Jiao J, Zhang J, Lu Y, Zhang L, Wan D, Duan L, Wu Y, Zhang B. Down-regulation of miR-125a-5p is associated with salivary adenoid cystic carcinoma progression via targeting p38/JNK/ERK signal pathway. Am J Transl Res. 2017;9(3):1101–13.PubMedPubMedCentral
16.
Xu Y, Huang Z, Liu Y. Reduced miR-125a-5p expression is associated with gastric carcinogenesis through the targeting of E2F3. Mol Med Rep. 2014;10(5):2601–8.PubMedCrossRef
17.
Nadine R, Hellmuth-Alexander M, Monika J, Hans-Joachim M, Ina W, Kurt M, Ergin K, Andreas E, Steffen W, Klaus J. Reference miRNAs for miRNAome analysis of urothelial carcinomas. PLoS ONE. 2012;7(6):e39309.CrossRef
18.
Chen D, Sun Q, Zhang L, Zhou X, Cheng X, Zhou D, Ye F, Lin J, Wang W. The lncRNA HOXA11-AS functions as a competing endogenous RNA to regulate PADI2 expression by sponging miR-125a-5p in liver metastasis of colorectal cancer. Oncotarget. 2017;8(41):70642–52.PubMedPubMedCentralCrossRef
19.
Vilquin P, Donini CF, Villedieu M, Grisard E, Corbo L, Bachelot T, Vendrell JA, Cohen PA. MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer. Breast Cancer Res. 2015;17(1):1–20.CrossRef
20.
Zheng H, Wu J, Shi J, Lu C, Wang Y, Sun Q, Zhang G, Zhao G. miR-125a-5p upregulation suppresses the proliferation and induces the cell apoptosis of lung adenocarcinoma by targeting NEDD9. Oncol Rep. 2017;38(3):1790–6.PubMedCrossRef
21.
Cao Y, Tan S, Tu Y, Zhang G, Liu Y, Li D, Xu S, Le Z, Xiong J, Zou W. MicroRNA-125a-5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression. Oncol Lett. 2018;15(4):5119–30.PubMedPubMedCentral
22.
Hagen K, Hagen F, Balys M, Beres T, Van-Wuyckhuyse B, Tabak L. Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family. J Biol Chem. 1998;273(42):27749–54.PubMedCrossRef
23.
Strous GJ. Initial glycosylation of proteins with acetylgalactosaminylserine linkages. P Natl Acad Sci USA. 1979;76(6):2694–8.CrossRef
24.
Rui-Qing P, Hai-Ying W, Hai-Fang L, Min L, Xin L, Hua T. MicroRNA-214 suppresses growth and invasiveness of cervical cancer cells by targeting UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7. J Biol Chem. 2012;287(17):14301–9.CrossRef
25.
26.
Brockhausen I. Pathways of O-glycan biosynthesis in cancer cells. Biochim Biophys Acta. 1999;1473(1):67–95.PubMedCrossRef
27.
Hua S, Li H, Liu Y, Zhang J, Cheng Y, Dai C. High expression of GALNT7 promotes invasion and proliferation of glioma cells. Oncol Lett. 2018;16:6307–14.PubMedPubMedCentral
28.
Sahasrabudhe NM, Lenos K, Horst JCV, Rodríguez E, Vliet SJV. Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3. Bio Chem. 2018;399(7):649–59.CrossRef
29.
Kudryavtseva AV, Lukyanova EN, Kharitonov SL, Nyushko KM, Krasheninnikov AA, Pudova EA. Bioinformatic identification of differentially expressed genes associated with prognosis of locally advanced lymph node-positive prostate cancer. J Bioinform Comput Biol. 2019;1:195003.
30.
Munkley J, Vodak D, Livermore KE, James K, Wilson BT, Knight B, McCullagh P, McGrath J, Crundwell M, Harries LW, Leung HY, Robson CN, Mills IG, Rajan P, Elliott DJ. Glycosylation is an Androgen-Regulated process essential for prostate cancer cell viability. E Bio Med. 2016;8:103–16.
31.
Yang L, Zeng C, Hu J, Yue P, Shan Y, Bing L, Li J. Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression. J Hematol Oncol. 2018;11(1):89–114.CrossRef
32.
Duan HF, Li XQ, Hu HY, Yu CL, Zhi C, Xue SM, Peng Y, Li PM, Wei Z, Zhen DY, Guo HN. Functional elucidation of miR-494 in the tumorigenesis of nasopharyngeal carcinoma. Tumour Biol. 2015;36(9):6679–89.PubMedPubMedCentralCrossRef
33.
Li Y, Chen D, Lu Jin, Zheng MS, Jia JL, Hong FD, Xiao QL, Zheng YQ, Min S, Liang CN, Shang QY. miR–30a–5p in the tumorigenesis of renal cell carcinoma: a tumor suppressive microRNA. Mol Med Rep. 2016;13(5):4085–94.PubMedCrossRef
34.
Kwon A, Lee HL, Woo KM, Ryoo HM, Baek JH. SMURF1 Plays a role in EGF-induced breast cancer cell migration and invasion. Mol Cells. 2013;36(6):548–55.PubMedPubMedCentralCrossRef
35.
Uhlmann S, Zhang JA, Mannsperger H, Riazalhosseini Y, Burmester S, Ward A, Korf U, Wiemann S, Sahin O. miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer. Oncogene. 2010;29(30):4297–306.PubMedCrossRef
36.
Barr S, Thomson S, Buck E, Russo S, Petti F, Sujka-Kwok I, Eyzaguirre A, Rosenfeld-Franklin M, Gibson NW, Miglarese M. Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clin Exp Metastasis. 2008;25(6):685–93.PubMedPubMedCentralCrossRef
37.
Muñoz JP, Carrillo-Beltrán D, Aedo-Aguilera V, Calaf GM, León O, Maldonado E, Tapia JC, Boccardo E, Ozbun MA, Aguayo F. Tobacco exposure enhances human papillomavirus 16 oncogene expression via EGFR/PI3K/Akt/c-Jun signaling pathway in cervical cancer cells. Front Microbiol. 2018;9:3022–56.PubMedPubMedCentralCrossRef
38.
Adefuye AO, Sales KJ, Katz AA. Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway. J Mol Signal. 2014;9(1):1–17.
39.
Hu X, Schwarz JK, Lewis JS, Huettner PC, Rader JS, Deasy JO, Grigsby PW, Wang X. A MicroRNA expression signature for cervical cancer prognosis. Cancer Res. 2010;70(4):1441–8.PubMedPubMedCentralCrossRef
40.
Jeong-Won L, Chel Hun C, Jung-Joo C, Young-Ae P, Seung-Jun K, Seung Yong H, Woo Young K, Tae-Joong K, Je-Ho L, Byoung-Gie K. Altered MicroRNA expression in cervical carcinomas. Clin Cancer Res. 2008;14(9):2535–42.CrossRef
41.
Li G, Ao S, Hou J, Lyu G. Low expression of miR-125a-5p is associated with poor prognosis in patients with gastric cancer. Oncol Lett. 2019;18:1483–90.PubMedPubMedCentral
42.
Ming M, Ying M, Ling M. miRNA-125a-5p inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting TP53 regulated inhibitor of apoptosis 1 and Bcl-2-like-2 protein. Exp Ther Med. 2019;18:1196.PubMedPubMedCentral
43.
Cao K, Fang Y, Wang H, Jiang Z, Guo L, Hu Y. The lncRNA HOXA11-AS regulates Rab3D expression by sponging miR-125a-5p promoting metastasis of osteosarcoma. Cancer Manag Res. 2019;11:4505–18.PubMedPubMedCentralCrossRef
44.
Zhang Y, Zhang D, Lv J, Wang S, Zhang Q. MiR-125a-5p suppresses bladder cancer progression through targeting FUT4. Biomed Pharmacother. 2018;108:1039–47.PubMedCrossRef
45.
Tang L, Zhou L, Wu S, Shi X, Jiang G, Niu S, Ding D. miR-125a-5p inhibits colorectal cancer cell epithelial-mesenchymal transition, invasion and migration by targeting TAZ. Onco Targets Ther. 2019;2:3481–9.CrossRef
46.
Sze Wan S, Ling F, Tatiana S, Zina Jeyapalan R, Xiangling Y, William D, Wei-Yang L, Xuan JW, Zhaoqun D, Yang BB. Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci. 2013;126(6):1517–30.CrossRef
47.
Wei L, Huiping M, Ji S. MicroRNA?34a/c function as tumor suppressors in Hep?2 laryngeal carcinoma cells and may reduce GALNT7 expression. Mol Med Rep. 2014;9(4):1293–8.CrossRef
48.
Gill DJ, Joanne C, Jamie S, Frederic B. Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes. J Cell Biol. 2010;189(5):843–58.PubMedPubMedCentralCrossRef
49.
Chia J, Tay F, Bard F. The GalNAc-T activation (GALA) pathway: drivers and markers. PLoS One. 2019;14:0214118.CrossRef
50.
Gaziel-Sovran A, Segura M, Dimicco R, Collins M, Hanniford D, Vega-Saenzdemiera E, Rakus J, Dankert J, Shang S, Kerbel R. miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. Cancer Cell. 2011;20(1):104–18.PubMedPubMedCentralCrossRef
51.
Sloan KE, Stewart JK, Treloar AF, Matthews RT, Jay DG. CD155/PVR enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics. Cancer Res. 2005;65(23):10930–7.PubMedCrossRef
52.
Zhang Y, Han CY, Duan FG, Fan XX, Yao XJ, Parks RJ, Tang YJ, Wang MF, Liu L, Tsang BK, Leung EL. p53 sensitizes chemoresistant non-small cell lung cancer via elevation of reactive oxygen species and suppression of EGFR/PI3K/AKT signaling. Cancer Cell Int. 2019;19:188–219.PubMedPubMedCentralCrossRef
Metadata
Title
miR-125a-5p post-transcriptionally suppresses GALNT7 to inhibit proliferation and invasion in cervical cancer cells via the EGFR/PI3K/AKT pathway
Authors
Qinxue Cao
Ning Wang
Lu Ren
Jun Tian
Shaoqin Yang
Hailing Cheng
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01209-8

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Primary research

Identification of the fatty acid synthase interaction network via iTRAQ-based proteomics indicates the potential molecular mechanisms of liver cancer metastasis

Primary research

Over-expression of CDX2 alleviates breast cancer by up-regulating microRNA let-7b and inhibiting COL11A1 expression

Primary research

MiR-596 activated by EP300 controls the tumorigenesis in epithelial ovarian cancer by declining BRD4 and KPNA4

Primary research

LncRNA TTN-AS1 promotes the progression of oral squamous cell carcinoma via miR-411-3p/NFAT5 axis

Primary research

Circ_0072083 interference enhances growth-inhibiting effects of cisplatin in non-small-cell lung cancer cells via miR-545-3p/CBLL1 axis

Correction

Correction to: Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits