Methylation and expression of miRNAs in precancerous lesions and cervical cancer with HPV16 infection

Jiménez‐Wences, Hilda; Martínez‐Carrillo, Dinorah Nashely; Peralta‐Zaragoza, Oscar; Campos-Viguri, Gabriela Elizabeth; Hernández-Sotelo, Daniel; Jiménez‐López, Marco Antonio; Muñoz-Camacho, José Guadalupe; Garzón-Barrientos, Víctor Hugo; Illades‐Aguiar, Berenice; Fernández‐Tilapa, Gloria

doi:10.3892/or.2016.4583

Cited by 45 publications

(36 citation statements)

References 40 publications

(64 reference statements)

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“…In the present study, qRT-PCR analysis demonstrated that miR-124 was significantly downregulated in CC tissue samples and cancer cell lines. This finding was also verified by a study suggesting that abnormal promoter methylation and downregulation of miR-124 is a common event during cervical carcinogenesis (9).…”

Section: Discussionsupporting

confidence: 66%

“…miR-124 is one of the most studied and best characterized miRNAs with pivotal roles in several malignant processes, including tumor proliferation, motility and angiogenesis (7). It has been reported that miR-124 promoter is heavily methylated in CC cell lines, thus contributing to its slight expression in human CC specimens (8,9). miR-124 was discovered to be involved in MALAT1-miR-124-RBG2 axis where it affects growth and invasion of high-risk human papillomavirus-positive CC cells (10).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-124 inhibits proliferation, invasion, migration and epithelial-mesenchymal transition of cervical carcinoma cells by targeting astrocyte-elevated gene-1

et al. 2016

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MicroRNA-124 (miR-124) was reported to be attenuated in human cervical cancer (CC) specimens. However, its role in CC remains elusive. In the present study, quantitative real-time PCR (qRT-PCR) analysis demonstrated that miR-124 expression is significantly downregulated in human CC tissues and several CC cell lines. Transfection of miR-124 mimics in CC cell lines HeLa and SiHa markedly inhibits cell proliferative, migratory and invasive capacities, as well as the epithelial-mesenchymal transition (EMT) process in vitro. Further studies have identified astrocyte-elevated gene-1 (AEG-1) as a direct target gene of miR-124. miR-124 downregulated AEG-1 expression through interaction with its 3'-untranslated regions (3'-UTRs), and miR-124 expression was inversely correlated with AEG-1 levels in CC specimens. Moreover, exogenous overexpression of AEG-1 significantly rescued the miR-124-induced inhibition of cell proliferation, migration and invasion, as well as the EMT process in HeLa cells. In conclusion, these findings suggested that miR-124 was able to suppress cell proliferation, invasion and migration, as well as the EMT process in cervical carcinomas through directly targeting AEG-1. miR-124 and AEG-1 may be potential therapeutic targets for the treatment of cervical carcinoma.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

MicroRNA-124 inhibits proliferation, invasion, migration and epithelial-mesenchymal transition of cervical carcinoma cells by targeting astrocyte-elevated gene-1

et al. 2016

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“…Emerging evidence shows that dysregulation of miRNAs plays a vital role in many biological processes, including proliferation, invasion and apoptosis (18). Hyper-methylation and reduced expression of anti-tumorigenic miRNAs’ promoters are associated with cancer progression in colorectal (19), chronic lymphocytic leukemia (20), cervical (21), breast (22), and gastric cancers (17,23). On the other hand, hypo-methylation of pro-oncogenic miRNAs’ promoters have been reported in hepatocellular carcinoma (24), pancreatic (25), and ERα positive breast cancers (26).…”

Section: Introductionmentioning

confidence: 99%

Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells

Shao

Chen

Peng

et al. 2018

Molecular Cancer Research

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The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, the regulation and role of miR-196b-5p in gastric cancer was investigated. Quantitative real-time RT-PCR (qPCR) demonstrated that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P<0.01). In addition, it was determined that HOXA10, a homeobox family member and host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P<0.001). Quantitative pyrosequencing methylation analysis, demonstrated significantly lower levels of DNA methylation at the HOXA10 promoter in gastric cancer, as compared to non-neoplastic gastric mucosa specimens. 5-Aza-2′-deoxycytidine treatment confirmed that demethylation of HOXA10 promoter induces the expression of HOXA10 and miR-196b-5p in gastric cancer cell model systems. Using the Tff1-KO mouse model of gastric neoplasia, hypo-methylation and overexpression of HOXA10 and miR-196b-5p in gastric tumors was observed, as compared to normal gastric mucosa from Tff1-WT mice. Mechanistically, reconstitution of TFF1 in human gastric cancer cells lead to an increased HOXA10 promoter methylation with reduced expression of HOXA10 and miR-196b-5p. Functionally, miR-196b-5p reconstitution promoted human gastric cancer cell proliferation and invasion in vitro. In summary, the current data demonstrates overexpression of miR-196b-5p in gastric cancer and suggests that TFF1 plays an important role in suppressing the expression of miR-196b-5p by mediating DNA methylation of the HOXA10 promoter. Loss of TFF1 expression may promote proliferation and invasion of gastric cancer cells through induction of promoter hypo-methylation and expression of the HOXA10/miR-196b-5p axis.

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“…In addition, DNA hypermethylation-associated repression of tumor suppressor genes has been reported to be essential for Ras-mediated transformation [26][27][28][29]. On the other hand, accumulating evidence shows that miRNA can be deregulated by epigenetic alterations such as aberrant DNA methylation in human cancer, including breast cancer [30][31][32][33][34][35][36][37][38][39]. Therefore, to test whether epigenetic alterations affect expression of miR-205, we treated cells with DNA methyltransferase (DNMT) inhibitor 5-aza-2 0 -deoxycytidine.…”

Section: Erbb2 Signaling Via Ras/raf/mek/erk Pathway Decreases Mir-20mentioning

confidence: 99%

ErbB2 signaling epigenetically suppresses microRNA‐205 transcription via Ras/Raf/MEK/ERK pathway in breast cancer

et al. 2017

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We previously reported that micro RNA ‐205 (miR‐205) is downregulated by overexpression of the receptor tyrosine kinase ErbB2 and that ectopic transfection of miR‐205 precursor decreases ErbB2 tumorigenicity in soft agar. In this study, we further analyzed the regulatory mechanisms linking ErbB2 overexpression and miR‐205 downregulation. In ErbB2‐overexpressing breast epithelial cells, miR‐205 expression was significantly increased by treatment with MEK inhibitor U0126 or PD 98059, Raf‐1 inhibitor ZM ‐336372, and ERK inhibitor SCH 772984, but PI 3K inhibitor LY 294002 and p38 MAPK inhibitor SB 203580 had no effect. We established breast epithelial cells overexpressing Raf CAAX , a constitutively active form of Raf‐1, and showed that overexpression of Raf CAAX dramatically reduced miR‐205 expression. In Raf CAAX ‐overexpressing cells, miR‐205 expression was also significantly increased by SCH 772984. Moreover, miR‐205 expression was significantly increased by treatment with DNA methyltransferase ( DNMT ) inhibitor 5‐aza‐2′‐deoxycytidine and expression of several DNMT family members was increased in both ErbB2‐ and Raf CAAX ‐overexpressing cells. DNA methylation analysis by bisulfite sequencing revealed that the putative miR‐205 promoters were predominantly hypermethylated in both ErbB2‐ and Raf CAAX ‐overexpressing cells. Reporter activity of the putative miR‐205 promoters was reduced in both ErbB2‐overexpressing and Raf CAAX ‐overexpressing cells. Together, these findings indicate that ErbB2 signaling epigenetically suppresses miR‐205 transcription via the Ras/Raf/ MEK / ERK pathway.

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Methylation and expression of miRNAs in precancerous lesions and cervical cancer with HPV16 infection

Cited by 45 publications

References 40 publications

MicroRNA-124 inhibits proliferation, invasion, migration and epithelial-mesenchymal transition of cervical carcinoma cells by targeting astrocyte-elevated gene-1

MicroRNA-124 inhibits proliferation, invasion, migration and epithelial-mesenchymal transition of cervical carcinoma cells by targeting astrocyte-elevated gene-1

Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells

ErbB2 signaling epigenetically suppresses microRNA‐205 transcription via Ras/Raf/MEK/ERK pathway in breast cancer

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