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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Primary research

Antisense oligonucleotides against microRNA-21 reduced the proliferation and migration of human colon carcinoma cells

Authors: Yi-Jing Tao, Yong-ju Li, Wen Zheng, Juan-juan Zhao, Meng-meng Guo, Ya Zhou, Na-lin Qin, Jing Zheng, Lin Xu

Published in: Cancer Cell International | Issue 1/2015

Login to get access

Abstract

Background

Colon carcinoma is one of the commonly tumors that threaten human beings as its highly morbidity and mortality. Recent evidences suggested that microRNA-21 (miR-21) played an important role in the development of colon carcinoma and might be a potential biological marker for the diagnosis and prognosis of colon carcinoma. However, the potential effect of miR-21 based therapeutic studies in colon carcinoma remains to be fully elucidated.

Methods

In present study, we constructed an eukaryotic expression vector encoding antisense oligonucleotides against miR-21 (termed as p-miR-21-ASO) and the expression of miRNA-21 in human colon cancer was detected by Real-time PCR. To assess its possible effect on the proliferation and migration capacity of human colon carcinoma cells in vitro, CCK-8 assay, colony formation assay and cell invasion, as well as migration assay, were performed respectively. Moreover, PTEN, one of target molecules of miRNA-21, was analyzed by Western blot and Fluorescence activated cell sorter assay. Finally, the transduction of AKT and ERK pathways in human colon carcinoma cells was determined by Western blot.

Results

We found that transiently transfection of p-miR-21-ASO could efficiently decrease the relative expression of miR-21 in human colon carcinoma HCT116 cells, accompanied by impaired proliferation and clone formation. Furthermore, we found that down-regulation of miR-21 also could significantly abrogate the invasion and migration capacity in vitro, as well as the expression of vascular endothelial growth factor which is critical for the metastatic capacity of colon carcinoma cells. Mechanistic evidence showed that down-regulation of miR-21 increased the expression of its target molecule PTEN in HCT116 cells. Finally, we revealed that the expression level of both phosphor-ERK1/2 and phosphor-AKT also were altered.

Conclusions

Therefore, our data suggested miR-21 ASO against miR-21 might be a useful strategy to alter the expression of miR-21 in colon carcinoma cells, which was helpful for the development of miR-21-based therapeutic strategies against clinical colon carcinoma.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Ward E, Hao Y, Thun M (2005) Trends in the leading causes of death in the United States, 1970–2002. JAMA 294(10):1255–1259PubMedCrossRef
2.
Jafri SH, Mills G (2013) Lifestyle modification in colorectal cancer patients: an integrative oncology approach. Future Oncol 9(2):207–218PubMedCrossRef
3.
Matsushita Y, Nakamori S, Seftor EA, Hendrix MJ, Irimura T (1991) Human colon carcinoma cells with increased invasive capacity obtained by selection for sialyl-dimeric LeX antigen. Exp Cell Res 196(1):20–25PubMedCrossRef
4.
Ciardiello F, Kim N, Saeki T, Dono R, Persico MG, Plowman GD et al (1991) Differential expression of epidermal growth factor-related proteins in human colorectal tumors. Proc Natl Acad Sci USA 88(17):7792–7796PubMedCentralPubMedCrossRef
5.
Liang B, Shahbaz M, Wang Y, Gao H, Fang R, Niu Z et al (2015) Integrinbeta6-targeted immunoliposomes mediate tumor-specific drug delivery and enhance therapeutic efficacy in colon carcinoma. Clin Cancer Res 21(5):1183–1195PubMedCrossRef
6.
Mannucci S, Ghin L, Conti G, Tambalo S, Lascialfari A, Orlando T et al (2014) Magnetic nanoparticles from Magnetospirillum gryphiswaldense increase the efficacy of thermotherapy in a model of colon carcinoma. PLoS One 9(10):e108959PubMedCentralPubMedCrossRef
7.
Li T, Leong MH, Harms B, Kennedy G, Chen L (2013) MicroRNA-21 as a potential colon and rectal cancer biomarker. World J Gastroenterol 19(34):5615–5621PubMedCentralPubMedCrossRef
8.
Yang CH, Yue J, Sims M, Pfeffer LM (2013) The curcumin analog EF24 targets NF-kappaB and miRNA-21, and has potent anticancer activity in vitro and in vivo. PLoS One 8(8):e71130PubMedCentralPubMedCrossRef
9.
Echevarria-Vargas IM, Valiyeva F, Vivas-Mejia PE (2014) Upregulation of miR-21 in cisplatin resistant ovarian cancer via JNK-1/c-Jun pathway. PLoS One 9(5):e97094PubMedCentralPubMedCrossRef
10.
Drusco A, Nuovo GJ, Zanesi N, Di Leva G, Pichiorri F, Volinia S et al (2014) MicroRNA profiles discriminate among colon cancer metastasis. PLoS One 9(6):e96670PubMedCentralPubMedCrossRef
11.
Roy S, Yu Y, Padhye SB, Sarkar FH, Majumdar AP (2013) Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21. PLoS One 8(7):e68543PubMedCentralPubMedCrossRef
12.
Nangia-Makker P, Yu Y, Vasudevan A, Farhana L, Rajendra SG, Levi E et al (2014) Metformin: a potential therapeutic agent for recurrent colon cancer. PLoS One 9(1):e84369PubMedCentralPubMedCrossRef
13.
Bestas R, Kaplan MA, Isikdogan A (2014) The correlation between serum VEGF levels and known prognostic risk factors in colorectal carcinoma. Hepatogastroenterology 61(130):267–271PubMed
14.
Szajewski M, Kruszewski WJ, Lakomy J, Ciesielski M, Kawecki K, Jankun J et al (2014) VEGF-C and VEGF-D overexpression is more common in left-sided and well-differentiated colon adenocarcinoma. Oncol Rep 31(1):125–130PubMed
15.
Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133(2):647–658PubMedCentralPubMedCrossRef
16.
Takei Y, Saga Y, Mizukami H, Takayama T, Ohwada M, Ozawa K et al (2008) Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice. Mol Cancer Ther 7(3):704–711PubMedCrossRef
17.
18.
Tian T, Nan KJ, Wang SH, Liang X, Lu CX, Guo H et al (2010) PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cells. Carcinogenesis 31(7):1211–1219PubMedCrossRef
19.
Harris VK, Coticchia CM, Kagan BL, Ahmad S, Wellstein A, Riegel AT (2000) Induction of the angiogenic modulator fibroblast growth factor-binding protein by epidermal growth factor is mediated through both MEK/ERK and p38 signal transduction pathways. J Biol Chem 275(15):10802–10811PubMedCrossRef
20.
Xia C, Meng Q, Cao Z, Shi X, Jiang BH (2006) Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression. J Cell Physiol 209(1):56–66PubMedCrossRef
21.
22.
Zhu S, Si ML, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282(19):14328–14336PubMedCrossRef
23.
Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S et al (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27(15):2128–2136PubMedCrossRef
24.
Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 283(2):1026–1033PubMedCrossRef
25.
26.
Zheng SR, Guo GL, Zhai Q, Zou ZY, Zhang W (2013) Effects of miR-155 antisense oligonucleotide on breast carcinoma cell line MDA-MB-157 and implanted tumors. Asian Pac J Cancer Prev 14(4):2361–2366PubMedCrossRef
27.
Xu L, Wen Z, Zhou Y, Liu Z, Li Q, Fei G et al (2013) MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway. Mol Biol Cell 24(1):42–55PubMedCentralPubMedCrossRef
28.
Li YJ, Zhang YX, Wang PY, Chi YL, Zhang C, Ma Y et al (2012) Regression of A549 lung cancer tumors by anti-miR-150 vector. Oncol Rep 27(1):129–134PubMed
29.
Qiang XF, Zhang ZW, Liu Q, Sun N, Pan LL, Shen J et al (2014) miR-20a promotes prostate cancer invasion and migration through targeting ABL2. J Cell Biochem 115(7):1269–1276PubMedCrossRef
30.
Li B, Ren S, Li X, Wang Y, Garfield D, Zhou S et al (2014) MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer. Lung Cancer 83(2):146–153PubMedCrossRef
31.
Fang L, Li H, Wang L, Hu J, Jin T, Wang J et al (2014) MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget 5(10):2974–2987PubMedCentralPubMed
32.
Yang TS, Yang XH, Chen X, Wang XD, Hua J, Zhou DL et al (2014) MicroRNA-106b in cancer-associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN. FEBS Lett 588(13):2162–2169PubMedCrossRef
33.
Jiang J, Zhang Y, Yu C, Li Z, Pan Y, Sun C (2014) MicroRNA-492 expression promotes the progression of hepatic cancer by targeting PTEN. Cancer cell Int 14(1):95PubMedCentralPubMedCrossRef
34.
Setia S, Nehru B, Sanyal SN (2014) The PI3K/Akt pathway in colitis associated colon cancer and its chemoprevention with celecoxib, a Cox-2 selective inhibitor. Biomed Pharmacother 68(6):721–727PubMedCrossRef
35.
Jagan IC, Deevi RK, Fatehullah A, Topley R, Eves J, Stevenson M et al (2013) PTEN phosphatase-independent maintenance of glandular morphology in a predictive colorectal cancer model system. Neoplasia 15(11):1218–1230PubMedCentralPubMedCrossRef
36.
Setia S, Nehru B, Sanyal SN (2014) Upregulation of MAPK/Erk and PI3K/Akt pathways in ulcerative colitis-associated colon cancer. Biomed Pharmacother 68(8):1023–1029PubMedCrossRef
37.
Auyeung KK, Mok NL, Wong CM, Cho CH, Ko JK (2010) Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells. Int J Mol Med 26(3):341–349PubMed
38.
Zhang Q, Ren W, Huang B, Yi L, Zhu H (2015) MicroRNA-183/182/96 cooperatively regulates the proliferation of colon cancer cells. Mol Med Rep 12(1):668–674PubMed
39.
Sun Y, Tian H, Wang L (2015) Effects of PTEN on the proliferation and apoptosis of colorectal cancer cells via the phosphoinositol-3-kinase/Akt pathway. Oncol Rep 33(4):1828–1836PubMed
40.
Zhiyong C, Wentong L, Xiaoyang Y, Ling P (2012) PTEN’s regulation of VEGF and VEGFR1 expression and its clinical significance in myeloid leukemia. Med Oncol 29(2):1084–1092PubMedCrossRef
41.
Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J et al (2005) The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev 19(17):2054–2065PubMedCentralPubMedCrossRef
42.
Fassan M, Pizzi M, Giacomelli L, Mescoli C, Ludwig K, Pucciarelli S et al (2011) PDCD4 nuclear loss inversely correlates with miR-21 levels in colon carcinogenesis. Virchows Archiv 458(4):413–419PubMedCrossRef
Metadata
Title
Antisense oligonucleotides against microRNA-21 reduced the proliferation and migration of human colon carcinoma cells
Authors
Yi-Jing Tao
Yong-ju Li
Wen Zheng
Juan-juan Zhao
Meng-meng Guo
Ya Zhou
Na-lin Qin
Jing Zheng
Lin Xu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0228-7

Other articles of this Issue 1/2015

Cancer Cell International 1/2015 Go to the issue

Primary research

Jacaric acid inhibits the growth of murine macrophage-like leukemia PU5-1.8 cells by inducing cell cycle arrest and apoptosis

Review

The role of death-associated protein 3 in apoptosis, anoikis and human cancer

Primary research

Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients

Primary research

Upregulated expression of DIXDC1 in intestinal-type gastric carcinoma: co-localization with β-catenin and correlation with poor prognosis

Primary research

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation

Primary research

RB mutation and RAS overexpression induce resistance to NK cell-mediated cytotoxicity in glioma cells
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