Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level

Wang, Dong; Sun, Xinlei; Yao, Wei; Liang, Hongwei; Yuan, Min; Jin, Fangfang; Chen, Xi; Liu, Yuan; Zhang, Chenyu; Liu, Limin; Zen, Ke

doi:10.1093/nar/gkx1254

Cited by 65 publications

(59 citation statements)

References 66 publications

(87 reference statements)

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“…101,104 Notably, nuclear miR-122 directly binds pri-miR-21 to inhibit maturation of the oncomiR miR-21, decreasing chemoresistance and HCC growth. 106 miR-21 is overexpressed in HCC and intrahepatic CCA. 107,108 miR-21 contributes to cancer cell growth, migration, and invasion by inhibiting PTEN.…”

Section: Micrornas Regulate Hcc Development By Functioning As Inflammmentioning

confidence: 98%

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

2019

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Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B and C and alcoholic and nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, adaptive immune cells, such as CD8+ T cells, Th17 cells, and B cells, can also stimulate HCC development. Thus, the role of the hepatic immune system in HCC development is a highly complex topic. This review highlights the role of cytokine signals, NF-κB, JNK, innate and adaptive immunity, and hepatic stellate cells in HCC and discusses whether these pathways could be therapeutic targets. The authors will also discuss cholangiocarcinoma and liver metastasis because biliary inflammation and tumor-associated stroma are essential for cholangiocarcinoma development and because primary tumor-derived inflammatory mediators promote the formation of a “premetastasis niche” in the liver.

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Section: Micrornas Regulate Hcc Development By Functioning As Inflammmentioning

confidence: 98%

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

2019

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“…The oncomiR miR-21 16,17,44,45 was previously confirmed to be involved in the proliferation of numerous types of cells and tumors. 19,46-50 miR-21 can also promote the proliferation of vascular smooth muscle cells and pulmonary artery smooth muscle cells.…”

Section: Discussionmentioning

confidence: 94%

“…The transfer of these functional molecules can mediate changes in metabolism or gene expression, [11][12][13] as evidenced by the intercellular regulation of tumor metastasis, antiviral immunology, and metabolism. [10][11][12]14,15 miR-21 (hsa-miR-21-5p) is an oncomiR located on chromosome 17 that is expressed widely in tumors, 16,17 where it promotes cell proliferation. miR-21 is considered an osteoblastic miRNA, with roles in bone differentiation and development, and osteoblast differentiation and mineralization.…”

Section: Introductionmentioning

confidence: 99%

Exosomal hsa-miR-21-5p derived from growth hormone-secreting pituitary adenoma promotes abnormal bone formation in acromegaly

Xiong

Tang

Fan

et al. 2020

Translational Research

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Growth hormone-secreting pituitary adenoma (GHPA), a benign endocrine tumor located in the base of the skull, results in acromegaly. In addition to the mass effect of the tumor itself in the sellar region, GHPA can lead to the overgrowth of almost every organ. Previous findings indicated that the processes underlying acromegaly were partly attributable to hyperactivity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. However, the mechanisms driving this syndrome remains largely unknown. Additionally, the roles of GHPA-derived exosomes, which contain functional microRNAs and proteins that manipulate target cell proliferation and differentiation in distal extremities, are also unknown. In this study, we demonstrated that GHPA exosomes promote bone formation in vitro and trabecula number in vivo. The mechanism of increased trabecula formation may be attributable to GHPA exosome-induced osteoblast proliferation via increased cell viability and DNA replication. We further discovered that exosomal hsa-miR-21-5p plays a distinct role from the GH/IGF-1 axis in these processes. Accordingly, the results of this study provide a novel mechanism whereby GHPA influences distal extremities and a new perspective for treating GHPA. (Translational Research 2020; 215:1À16) Abbreviations: ALP = alkaline phosphatase; ARS = Alizarin Red Staining; BCIP = 5-bromo-4-chloro-3indolyl-phosphate; cDNA = complementary DNA; CCK-8 = Cell Counting Kit 8; CM = conditioned medium; CPC = cetylpyridinium chloride solution; CT = computed tomography; DAPI = 4 0 ,6-diamidino-2-phenylindole; DMEM = Dulbecco's modified Eagle's medium; ECMP = extracellular matrix protein; EDTA = ethylenediaminetetraacetic acid; EdU = 5-ethynyl-2 0 -deoxyuridine; ELISA = enzyme-linked immunosorbent assay; FBS = fetal bovine serum; FITC = fluorescein isothiocyanate; GH = growth hormone; GHPA = growth hormone-secreting pituitary adenoma; HE = hematoxylin and eosin; HRCT = high-resolution computed tomography; IGF-1 = insulin-like growth factor-1; IHC = immunohistochemistry; miRNA = microRNA; MVB = microvesicular bodies; NBT = nitro-blue-tetrazolium; NFPA = nonfunctioning pituitary adenoma; OCN = osteocalcin; PBS = phosphate-buffered saline; PCNA = proliferating cell nuclear antigen; PROB = primary rat osteoblast; qRT-PCR = quantitative real-time polymerase chain reaction; RT = room temperature; SD = standard deviation; siRNA = small-interfering RNA; TSG101 = tumor-susceptibility gene 101This study provides evidence that exosomal miR-21 derived from GHPA cells can manipulate osteoblast proliferation, osteocalcin and collagen I synthesis, and bone formation through a pathway distinct from the traditional GH/IGF-1 axis. This finding may serve as a foundation for developing new therapeutics that target GHPA.

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“…MicroRNAs (miRNAs) are novel, highly stable, and abundant endogenous noncoding RNAs. With the development of high-throughput sequencing and bioinformatics analysis, an increasing number of miRNAs has been identified and confirmed to regulate the development and progression of various human cancers in recent years [28,29] . However, few miRNAs have been functionally and mechanistically characterized with regard to gastric cancer, and the biological functions of most miRNAs have yet to be explored.…”

Section: Discussionmentioning

confidence: 99%

MiR-203 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by down-regulating fibroblast growth factor 2

Zhao

Chen

et al. 2020

Preprint

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Background: Aberrant fibroblast growth factor 2 (FGF2) expression is a major cause of poor prognosis in pancreatic cancer. MiR-203 is a newly discovered microRNA (miRNA) that can affect the biological behavior of tumors. This study investigated whether miR-203 can regulate FGF2 expression and its role in pancreatic cancer cell proliferation, apoptosis, invasion, and migration.Methods: MiR-203 expression in different cell lines was examined by qRT-PCR, followed by the establishment of knockdown and overexpression cell models. We used the CCK-8 assay to examine cell proliferation and the annexin V-APC/7-AAD doublestaining method to detect apoptosis. In addition, we used wound healing and transwell assays to investigate the effects of miR-203 on the migration and invasion of pancreatic cancer cells. The effects of miR-203 knockdown and overexpression on FGF2 mRNA expression were detected by qRT-PCR. We also overexpressed FGF2 and examined the effects of FGF2 overexpression on the proliferation, apoptosis, invasion, and migration of pancreatic cancer cells. The binding of miR-203 to FGF2 was assessed by a luciferase reporter assay. Results:We found that the miR-203 expression level was significantly down-regulated in pancreatic cancer cells compared to normal pancreatic cells. Functionally, the knockdown of miR-203 inhibited cell proliferation and increased apoptosis. Equally important, miR-203 reduced the migration and invasion of pancreatic cancer cells. In addition, we found that miR-203 overexpression inhibited FGF2 expression in pancreatic cancer cells by qRT-PCR. FGF2 overexpression significantly affected the proliferation, invasion, and metastasis of pancreatic cancer cells. Mechanistically, miR-203 base-paired with the FGF2 mRNA, resulting in the knockdown of the FGF2 mRNA and the down-regulation of the FGF2 protein. Conclusions:MiR-203 inhibits FGF2 expression, regulates the proliferation of pancreatic cancer cells, and inhibits the invasion and metastasis of pancreatic cancer cells.

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Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level

Cited by 65 publications

References 66 publications

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

Exosomal hsa-miR-21-5p derived from growth hormone-secreting pituitary adenoma promotes abnormal bone formation in acromegaly

MiR-203 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by down-regulating fibroblast growth factor 2

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