MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation

Jiang, Jianxin; Zhang, Yi; Guo, Yuting; Yu, Chao-Ming; Chen, Meiyuan; Li, Zhu-Zhu; Tian, Se; Sun, Chengyi

doi:10.18632/oncotarget.3438

Cited by 37 publications

(32 citation statements)

References 42 publications

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“…In another study, miR-3127 was shown to repress NSCLC cell proliferation and invasion via the direct regulation of oncogene ABL1, leading to the inhibition of the RAS/ERK pathway (Sun et al, 2014). However, there were still conflicting reports that miR-3127 actually acted as an oncogene in hepatocellular carcinoma by activating AKT/FOXO1 signaling, via directly targeting the 3 -UTR of PHLPP1/2 (Jiang et al, 2015). The precise mechanisms of action and target genes of miR-3127 in BCA are not clear.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, microRNAs (miRNAs) are small endogenous non-coding RNAs composed of approximately 19-24 nucleotides that regulate target genes posttranscriptionally (Dong et al, 2017), and miRNAs play key roles in the modulation of tumor growth and metastasis (Dong et al, 2017(Dong et al, , 2018b. It has been reported that miR-3127 acts as either a tumor suppressor or an oncogene in cancers, such as glioma (Pan et al, 2019), lung cancer (Sun et al, 2014;Yang et al, 2018) and hepatocellular carcinoma (Jiang et al, 2015). Downregulation of miR-3127-5p promotes epithelial-mesenchymal transition through activating the Wnt/FZD4/β-catenin pathway in nonsmall-cell lung cancer (Yang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Downregulation of miR-3127-5p promotes epithelial-mesenchymal transition through activating the Wnt/FZD4/β-catenin pathway in nonsmall-cell lung cancer (Yang et al, 2018). However, miR-3127 promotes the proliferation and tumorigenesis in hepatocellular carcinoma by inducing the AKT/FOXO1 signaling (Jiang et al, 2015). Recent investigation has shown that several lncRNAs (including GACAT3, FOXD2-AS1, and LINC00319) modulate the malignant properties of tumor cells through sponging miR-3127 (Pan et al, 2019;Yang et al, 2020;Zhang and Chen, 2020).…”

Section: Introductionmentioning

confidence: 99%

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LINC00319-Mediated miR-3127 Repression Enhances Bladder Cancer Progression Through Upregulation of RAP2A

Wang

Meng

2020

Front. Genet.

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Recent studies suggested that microRNA-3127 (miR-3127) was dysregulated in multiple tumor types and has important roles in tumorigenesis and cancer progression. However, its biological roles and the mechanisms that regulate its expression in bladder cancer (BCA) remain to be determined. The expression level of miR-3127 was measured in BCA tissues and its cellular functions were examined using both in vitro and in vivo experiments. The interaction between miR-3127 and long non-coding RNA (lncRNA) LINC00319 was explored using RNA immunoprecipitation assay and luciferase reporter assays. We showed that miR-3127 expression was significantly downregulated in human BCA tissues and BCA cell lines. Lower miR-3127 levels were associated with worse survival in BCA patients. The overexpression of miR-3127 impaired BCA cell proliferation and invasion, and the knockdown of miR-3127 enhanced BCA cell proliferation and invasion in vitro. Importantly, miR-3127 was able to suppress cell growth in vivo. We demonstrated that miR-3127 repressed the proliferation and invasion of BCA cells though directly targeted the 3-UTR of RAP2A, which served as a novel oncogene in BCA cells. The suppression of cell proliferation and invasion caused by miR-3127 overexpression could be partially abrogated by ectopic expression of RAP2A. Furthermore, high expression of LINC00319 was correlated with adverse survival in BCA patients. LINC00319 could bind directly with miR-3127 and inhibited its expression, and the tumor-promoting effects of LINC00319 could be reversed by re-expression of miR-3127 in BCA cells. Our findings indicated that lncRNA LINC00319-mediated miR-3127 repression promotes BCA progression through the upregulation of RAP2A. The re-introduction of miR-3127 or inhibition of LINC00319 might represent a promising therapeutic strategy for BCA treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LINC00319-Mediated miR-3127 Repression Enhances Bladder Cancer Progression Through Upregulation of RAP2A

Wang

Meng

2020

Front. Genet.

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“…In hepatocellular carcinoma (HCC), miR-331-3p, which targets both PHLPP1 and PHLPP2, is significantly over-expressed [35]. miR-3127 is also over-expressed in HCC, and can function to suppress expression of not only PHLPP1 and PHLPP2, but also Inositol Polyphosphate Phosphatase 4A (INPP4A) and Inositol Polyphosphate-5-Phosphatase J (INPP5J) [36], two enzymes involved in inositol metabolism. miR-205 has been shown to target the 3′UTR of PHLPP2 and Phosphatase and Tensin Homologue (PTEN), and is in a region of the genome that is frequently amplified in non-small cell lung cancer (NSCLC) [37].…”

Section: Regulation Of Phlpp Expressionmentioning

confidence: 99%

PHLPPing through history: a decade in the life of PHLPP phosphatases

Grzechnik

Newton

2016

Biochemical Society Transactions

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In the decade since their discovery, the PH domain Leucine rich repeat Protein Phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200,000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome. Both PHLPP1 and PHLPP2 are commonly deleted in human cancers, supporting a tumor suppressive role. Conversely, the levels of one isozyme, PHLPP1, are elevated in diabetes. Thus, mechanisms to correctly control PHLPP activity in cells are critical for normal cellular homeostasis. This review summarizes the known functions of PHLPP and its role in disease.

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“…PI3K is a kinase that is involved in multiple cellular signaling pathways. As regards Akt, it is an important factor in the downstream of PI3K (20). It is able to regulate cell proliferation and prevent cell apoptosis.…”

Section: Overexpression Of Microrna-133b Is Associated With the Incrementioning

confidence: 99%

Overexpression of microRNA-133b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy: Involvement of the EGFR/PI3K/Akt/mTOR signaling pathway

et al. 2017

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The aim of the present study was carried out to investigate the association of microRNA-133b (miRNA-133b) expression with the prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. In the present study, the expression of miRNA-133b in HCC tissues was determined to be lower than that noted in the adjacent normal tissues. Overall and disease-free survival of the HCC patients with high miRNA-133b expression was observably extended, compared with the HCC patients with low miRNA‑133b expression. Moreover, the overexpression of miRNA-133b inhibited cell proliferation, increased lactate dehydrogenase (LDH) activity, induced apoptosis and promoted caspase‑3/-8 activities and Bax/Bcl-2 protein expression in HCC cells, whereas the protein expression of epidermal growth factor receptor (EGFR) was significantly decreased. The overexpression of miRNA-133b significantly suppressed PI3K, phosphorylated (p)-Akt and p-mTOR protein expression in HCC cells. GW2974, an EGFR inhibitor, suppressed the protein expression of EGFR, inhibited cell proliferation, increased LDH activity, induced apoptosis and promoted caspase-3/-8 activities and Bax/Bcl-2 protein expression, downregulated PI3K, p-Akt and p-mTOR protein expression in the transfected HCC cells overexpressing miRNA-133b. Taken together, our results indicate that the overexpression of miRNA-133b is associated with the increased survival of HCC patients after curative hepatectomy. The effects of miRNA-133b in HCC are mediated through the EGFR/PI3K/Akt/mTOR signaling pathway.

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MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation

Cited by 37 publications

References 42 publications

LINC00319-Mediated miR-3127 Repression Enhances Bladder Cancer Progression Through Upregulation of RAP2A

LINC00319-Mediated miR-3127 Repression Enhances Bladder Cancer Progression Through Upregulation of RAP2A

PHLPPing through history: a decade in the life of PHLPP phosphatases

Overexpression of microRNA-133b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy: Involvement of the EGFR/PI3K/Akt/mTOR signaling pathway

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