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Target Concepts:
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Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Various cancer stem cell (CSC) biomarkers have been identified for
hepatocellular carcinoma
(
HCC
), but little is known about the implications of heterogeneity and shared molecular networks within the CSC population. Through miRNA profile analysis in an
HCC
cohort (
n
= 241) for five groups of CSC
+
HCC
tissues, i.e., EpCAM
+
, CD90
+
, CD133
+
, CD44
+
, and CD24
+
HCC
, we identified a 14-miRNA signature commonly altered among these five groups of CSC
+
HCC
. miR-192-5p, the top-ranked CSC miRNA, was liver-abundant and -specific and markedly downregulated in all five groups of CSC
+
HCC
from two independent cohorts (
n
= 613). Suppressing miR-192-5p in
HCC
cells significantly increased multiple CSC populations and CSC-related features through targeting
PABPC4
. Both
TP53
mutation and hypermethylation of the mir-192 promoter impeded transcriptional activation of miR-192-5p in
HCC
cell lines and primary CSC
+
HCC
. This study reveals the circuit from hypermethylation of the mir-192 promoter through the increase in
PABPC4
as a shared genetic regulatory pathway in various groups of primary CSC
+
HCC
. This circuit may be the driver that steers liver cells toward hepatic CSC cells, leading to hepatic carcinogenesis. SIGNIFICANCE: miR-192-5p and its regulatory pathway is significantly abolished in multiple groups of
HCC
expressing high levels of CSC markers, which may represent a key event for hepatic carcinogenesis.
...
PMID:miR-192-5p Silencing by Genetic Aberrations Is a Key Event in Hepatocellular Carcinomas with Cancer Stem Cell Features. 3053 Aug 15
Hepatocellular carcinoma
(
HCC
) is a malignancy found at high frequency around the world. Unfortunately, the scarcity of effective early diagnostic methods invariably results in poor outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the progression of
hepatocellular carcinoma
(
HCC
). A novel lncRNA RP11-286H15.1(OTTHUMG00000186042) has been identified and associated with
HCC
; however, the potential role of RP11-286H15.1 in
HCC
remains undefined. The transcript abundance of RP11-286H15.1 in 80 pairs of
HCC
samples and cell lines was evaluated by qRT-PCR analysis. The functional role of RP11-286H15.1 in
HCC
was tested in vivo and in vitro. The mechanisms underlying the role of RP11-286H15.1 in
HCC
were explored by RNA pulldown, transcriptome sequencing, and RNA immunoprecipitation (RIP), ubiquitination and fluorescence in situ hybridization (FISH) assays as well as Western blot analysis. The qRT-PCR and FISH assays revealed that RP11-286H15.1 was significantly decreased in
HCC
, and implied a shorter survival time. RP11-286H15.1 overexpression inhibited
HCC
cell proliferation and metastasis in vitro and in vivo, whereas RP11-286H15.1 knockdown produced the opposite results. Furthermore, we confirmed that RP11-286H15.1 (620-750 nucleotides) binds to poly(A) binding protein 4 (
PABPC4
) and promotes its ubiquitination, thus, reducing the stability of TRIM37 and CDC27 mRNAs. Our study demonstrates that a novel lncRNA, RP11-286H15.1, represses
HCC
progression by promoting
PABPC4
ubiquitination. These findings highlight potential therapeutic targets for
HCC
.
...
PMID:A novel long non-coding RNA RP11-286H15.1 represses hepatocellular carcinoma progression by promoting ubiquitination of PABPC4. 3325 99
