RETRACTED ARTICLE: MicroRNA-1468 promotes tumor progression by activating PPAR-γ-mediated AKT signaling in human hepatocellular carcinoma

Chen

et al. 2019

Clin Exp Pharma Physio

Self Cite

Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR-627-5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR-627-5p in HCC progression remains unclear yet. In our present study, miR-627-5p was determined to be low-expressed in HCC tissues and cell lines. Furthermore, miR-627-5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR-627-5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR-627-5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC-7721 cells. Conversely, miR-627-5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR-627-5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR-627-5p. MiR-627-5p overexpression reduced, whereas miR-627-5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR-627-5p and 3′UTR of BCL3.The expression of BCL3 protein was negatively correlated with miR-627-5p level in HCC tissues. More importantly, re-expression of BCL3 partially reversed miR-627-5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR-627-5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment. K E Y W O R D SBCL3, hepatocellular carcinoma, miR-627-5p, proliferation, tumour growth

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator

Chen

et al. 2019

Clin Exp Pharma Physio

Self Cite

J Cellular Molecular Medi

“…Accumulating studies have found that miRNAs are aberrantly expressed and dysfunctional in HCC . Recently, miRNAs have been shown to be associated with diagnosis, development, progression and prognosis of human HCC . miR‐301b‐3p is recently recognized as a cancer‐related miRNA.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐301b‐3p contributes to tumour growth of human hepatocellular carcinoma by repressing vestigial like family member 4

Guo

Yao

Zhu

et al. 2019

Self Cite

Micro RNA s (mi RNA s) are key regulators in the tumour growth and metastasis of human hepatocellular carcinoma ( HCC ). Increasing evidence suggests that miR‐301b‐3p functions as a driver in various types of human cancer. However, the expression pattern of miR‐301b‐3p and its functional role as well as underlying molecular mechanism in HCC remain poorly known. Our study found that miR‐301b‐3p expression was significantly up‐regulated in HCC tissues compared to adjacent non‐tumour tissues. Clinical association analysis revealed that the high level of miR‐301b‐3p closely correlated with large tumour size and advanced tumour‐node‐metastasis stages. Importantly, the high miR‐301b‐3p level predicted a prominent poorer overall survival of HCC patients. Knockdown of miR‐301b‐3p suppressed cell proliferation, led to cell cycle arrest at G2/M phase and induced apoptosis of Huh7 and Hep3B cells. Furthermore, miR‐301b‐3p knockdown suppressed tumour growth of HCC in mice. Mechanistically, miR‐301b‐3p directly bond to 3′ UTR of vestigial like family member 4 ( VGLL 4) and negatively regulated its expression. The expression of VGLL 4 mRNA was down‐regulated and inversely correlated with miR‐301b‐3p level in HCC tissues. Notably, VGLL 4 knockdown markedly repressed cell proliferation, resulted in G2/M phase arrest and promoted apoptosis of HCC cells. Accordingly, VGLL 4 silencing rescued miR‐301b‐3p knockdown attenuated HCC cell proliferation, cell cycle progression and apoptosis resistance. Collectively, our results suggest that miR‐301b‐3p is highly expressed in HCC . miR‐301b‐3p facilitates cell proliferation, promotes cell cycle progression and inhibits apoptosis of HCC cells by repressing VGLL 4.

“…This miRNA has been implicated in different cancer types [36, 37] and the latter pathway may indicate a potential mechanism for this. In fact, MIR1468 was recently shown to promote tumor progression by activating PPAR- γ -mediated Akt signaling in hepatocellular carcinoma [38].…”

Section: Resultsmentioning

confidence: 99%

PUMA: PANDA Using MicroRNA Associations

Kuijjer

Fagny

Marin

et al. 2019

Preprint

Conventional methods to analyze genomic data do not make use of the interplay between multiple 19 factors, such as between microRNAs (miRNAs) and the mRNA transcripts they regulate, and 20 thereby often fail to identify the cellular processes that are unique to specific tissues. We developed 21 PUMA (PANDA Using MicroRNA Associations), a computational tool that uses message passing to 22 integrate a prior network of miRNA target predictions with protein-protein interaction and target 23 gene co-expression information to model genome-wide gene regulation by miRNAs. We applied 24