Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2

Liu, Rui Fang; Xu, Xinlin; Huang, Jian; Fei, Qian Lan; Chen, Fei; Li, Yan Dong; Han, Ze‐Guang

doi:10.1016/j.canlet.2012.10.027

Cited by 42 publications

(34 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, a recent study shows that downregulation of MIR517C facilitates hepatocellular carcinoma cell growth. 22 In our present study, we provided further evidence that MIR517C could act as an "autophagamiR" in GBM; perhaps its function will not only regulate autophagy but also the EMT. Further studies are required to examine these relationships and for the development of potential therapeutic strategies for the treatment of GBM.…”

Section: Discussionsupporting

confidence: 58%

“…21 In another publication, downregulation of MIR517A and MIR517C promotes the proliferation of hepatocellular carcinoma cells. 22 In estrogen receptor (ER)-positive breast cancer, about 50 of the miRNAs within the C19MC cluster were found to be significantly upregulated in chemoresistant cells. Among these miRNAs, MIR519A regulates cell viability and cell cycle progression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MIR517Cinhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation

Xiao

Liu

et al. 2015

Autophagy

View full text Add to dashboard Cite

(2015) MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation, Autophagy, 11:12, 2213-2232, DOI: 10.1080/15548627.2015 LG, low glucose; MAP1LC3B/LC3B, microtubuleassociated protein 1 light chain 3B; MU, mutation; NC, negative control; NSC, neural stem cell; oe, overexpressing; OS, overall survival; PFS, progression-free survival; qRT-PCR, quantitative real-time reverse transcription polymerase chain reaction; SNAI2, Slug (snail family zinc finger 2); SNAI1, snail (snail family zinc finger 1); TEM, transmission electron microscopy; TMZ, temozolomide; VIM, vimentin; WT, wild type; ZEB1, zinc finger E-box binding homeobox 1.The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of MIR517C/miR-517c, which belongs to the C19MC microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that MIR517C was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), MIR517C degraded KPNA2 (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) TP53, but not in U251 cells harboring mutant (MU) TP53. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by MIR517C in U87 cells. Compared with MIR517C overexpression, MIR517C knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in TP53 +/+ and TP53 -/-HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT TP53 GBM cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.

show abstract

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

MIR517Cinhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation

Xiao

Liu

et al. 2015

Autophagy

View full text Add to dashboard Cite

show abstract

“…COBRA and bisulfite sequencing analysis further confirmed that the miR-520c regulatory region is hypermethylated in CRC cell lines. This finding is in line with previously described epigenetic silencing of the C19MC cluster members in HCC and gastric cancer [43, 44]. Loss of methylation in its regulatory region increases the miR-520c-3p expression and inhibits its target gene S100A4 protein amount after 5-Aza-treament in comparison to DMSO controls.…”

Section: Discussionsupporting

confidence: 92%

Epigenetic silencing of miR-520c leads to induced S100A4 expression and its mediated colorectal cancer progression

et al. 2017

View full text Add to dashboard Cite

The S100 calcium-binding protein A4 (S100A4) induces epithelial mesenchymal transition, migration, invasion, angiogenesis and metastasis. Its induced expression in several cancer types correlates with poor prognosis. Apart from the functional and transcriptional regulatory aspects of S100A4, its post-transcriptional regulation is not yet clearly elucidated. In this study, we show that microRNAs (miR) miR-505-5p and miR-520c-3p target the 3′-UTR of S100A4 and inhibits its expression and its mediated migration and invasion. 5-Aza treatment significantly increased miR-520c-3p expression and reduced the S100A4 protein amounts. The upstream promoter region of miR-520c is hypermethylated irrespective of the metastasis status of colorectal cancer (CRC) patient tissues and in all analyzed CRC cell lines. Moreover, in a cohort of CRC patient specimen (n = 59), miR-520c-3p was significantly downregulated. miR-520c-3p stably expressing HCT116 cells showed a reduced metastasis formation in livers after implanting in mice spleen. Taken together, our findings demonstrate that S100A4 is post-transcriptionally regulated by tumor suppressor miRs, miR-505c-5p and miR-520c-3p, and particularly miR-520c-3p expression is epigenetically silenced in CRC.

show abstract

“…Interestingly, their expression drops considerably when these cells differentiate (Ren et al , 2009; Stadler et al , 2010), which may indicate a role in the maintenance of an undifferentiated state. Furthermore, several reports indicate that certain C19MC miRNAs are aberrantly expressed in specific tumors, possibly reflecting reactivation of the C19MC cluster as the consequence of chromosomal rearrangement or epigenetic modifications (Saito et al , 2009; Tsai et al , 2009; Rippe et al , 2010; Liu et al , 2013). Li and colleagues showed that the C19MC locus was frequently amplified in certain pediatric brain tumors and suggested that members of this family of miRNAs had oncogenic properties in vitro and in vivo (Li et al , 2009).…”

Section: Other Functions Of C19mc Mirnasmentioning

confidence: 99%

“…In contrast, miR-519, a C19MC miRNA, was shown to exhibit strong tumor-suppressive activities (Marasa et al , 2010; Abdelmohsen et al , 2012). Two other C19MC members, miR517a and miR-517c, were recently implicated in inhibition of cell proliferation and tumor-suppressing activity (Liu et al , 2013). …”

Section: Other Functions Of C19mc Mirnasmentioning

confidence: 99%

The role of trophoblastic microRNAs in placental viral infection

Mouillet¹,

Ouyang²,

Bayer³

et al. 2014

Int. J. Dev. Biol.

View full text Add to dashboard Cite

During the past decade, various types of small non-coding RNAs were found to be expressed in all kingdoms and phyla of life. Intense research efforts have begun to shed light on their biological functions, although much remains to be determined in order to fully characterize their scope of biological action. Typically, small RNAs provide sequence specificity to a protein complex that is driven to silence a long target RNA. MicroRNAs (miRNAs) are small RNAs that are coded in the genome of most eukaryotes, and contribute to the cellular identity by regulating cell-specific gene networks by translational repression or degradation of mRNA. These effects commonly fine-tune gene expression associated with developmental or environmental cues. Different cell types can be characterized by their distinctive cellular miRNA landscape. The human placenta expresses a unique set of miRNAs, a high proportion of which is derived from a large cluster located on chromosome 19, (termed chromosome 19 miRNA cluster, or C19MC). Interestingly, a fraction of these placenta-enriched miRNAs are released to the extracellular environment through exosomes that were recently found to induce an antiviral immunity. In this review, we explore relevant placental viral infections and discuss the antiviral role of exosome-packaged placental C19MC miRNAs in this context.

show abstract

Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2

Cited by 42 publications

References 42 publications

MIR517Cinhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation

MIR517Cinhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation

Epigenetic silencing of miR-520c leads to induced S100A4 expression and its mediated colorectal cancer progression

The role of trophoblastic microRNAs in placental viral infection

Contact Info

Product

Resources

About