MiR-875-5p inhibits hepatocellular carcinoma cell proliferation and migration by repressing astrocyte elevated gene-1 (AEG-1) expression

Hu, Chen; Cui, Shichang; Zheng, Jingwu; Yin, Tian; Lv, Junsheng; Jiang, Long; Zhang, Wenwen; Wang, Xun; Sheng, Shoupeng; Zhang, Honghai; Sun, Yu; Wang, Hongguang; Liu, Cong

doi:10.21037/tcr.2018.01.22

Cited by 7 publications

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“…The main challenge of liver cancer treatment is recurrence and metastasis in the liver, which leads to a poor prognosis of liver cancer patients ( 3 ). MicroRNA is a class of non-coding RNA of 20 to 22 nucleotides, which can effectively regulate various biological processes, including cell proliferation, migration, differentiation, and apoptosis ( 4 ). The uncontrolled expression of microRNA is closely related to the pathogenesis of cancer, and it may act as a tumor suppressor gene or oncogene to promote the occurrence and development of liver cancer ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

Han¹,

Li²,

Cao³

2020

Transl Cancer Res TCR

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Background This study aims to investigate the effect of miR-212-5p overexpression targeting suppressor of cytokine signaling 5 (SOCS5) on the malignant proliferation of liver cancer cells HepG2 and tumor formation in nude mice with transplanted tumors. Methods Luciferase reporter assay was used to detect the targeted relationship between miR-212-5p and SOCS5, and SOCS5 was overexpressed by the SOCS5 pcDNA vector. MiR-212-5p mimic and pc DNA-SOCS5 were transfected into liver cancer HepG2 cells alone or in combination, and the cells were randomly divided into four groups, the control group, mimic group, SOCS5 group and mimic + SOCS5 group for subsequent experiments. The orthotopic xenograft mouse models were established by using HepG2 cells in BALB/c athymic nude mice. Results The results showed that there was a direct targeting relationship between miR-212-5p and SOCS5. Compared with the control group, the clone formation rate, the levels of Ki67, and proliferating cell nuclear antigen (PCNA) protein in the mimic group were significantly lower (P<0.05), but the apoptosis rate was significantly higher (P<0.05). The ratio of Bax/Bcl-2, cleaved Caspase-3/Caspase-3, and cleaved Caspase-9/Caspase-9 was significantly higher (P<0.05), while the ratios of p-phosphatidylinositol 3 kinase (PI3K)/PI3K, p- Protein kinase B (AKT)/AKT, and p-mammalian target of rapamycin (mTOR)/mTOR were significantly reduced (P<0.05). In the SOCS5 group, the result was reversed. Interesting, In the mimic+SOCS5 group the clone formation rate, the protein levels of Ki67, and PCNA were significantly decreased (P<0.05) while the apoptosis rate was significantly increased (P<0.05). The ratio of Bax/Bcl-2, cleaved Caspase-3/Caspase-3, and cleaved Caspase-9/Caspase-9 was significantly increased (P<0.05). The ratios of p-PI3K/PI3K, p-Akt/AKT, and p-mTOR/mTOR were significantly reduced (P<0.05). In vivo, The level of miR-212-5p was significantly increased, with SOCS5 decreased (P<0.05). Furthermore, the number of Ki67 positive cells was significantly reduced (P<0.05), and the apoptosis rate increased significantly (P<0.05). Additionally, the ratio of p-PI3K/PI3K, P-AKT/AKT, P-mTOR/mTOR decreased significantly (P<0.05). Conclusions miR-212-5p overexpression down-regulated SOCS5 could inhibit the malignant proliferation of HCC cells HepG2 and tumor formation in nude mice with transplanted tumors.

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Section: Introductionmentioning

confidence: 99%

The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

Han¹,

Li²,

Cao³

2020

Transl Cancer Res TCR

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“…One such miRNA is miR-195, a well documented miRNA playing a role in cancer associated pathways is also involved in inhibition of AEG-1 activity eventually restricting cell proliferation in HCC [125]. HCC progression could be further restricted by AEG-1 inhibition, not just by miR-195, but also miR-875-5p [126]. Similarly, in HCC exhibiting higher sorafenib resistance, the condition could be partially reversed by the degradation of AEG-1 through interaction with miR-375 in the cancerous cells [127], hence paving way for better sorafenib treatment in HCC patients.…”

Section: Micrornas and Silencing Rna As Effective Aeg-1 Inhibitorsmentioning

confidence: 99%

Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review

Sriramulu

Sun

Malayaperumal

et al. 2021

Cells

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Tumor breakthrough is driven by genetic or epigenetic variations which assist in initiation, migration, invasion and metastasis of tumors. Astrocyte elevated gene-1 (AEG-1) protein has risen recently as the crucial factor in malignancies and plays a potential role in diverse complex oncogenic signaling cascades. AEG-1 has multiple roles in tumor growth and development and is found to be involved in various signaling pathways of: (i) Ha-ras and PI3K/AKT; (ii) the NF-κB; (iii) the ERK or mitogen-activated protein kinase and Wnt or β-catenin and (iv) the Aurora-A kinase. Recent studies have confirmed that in all the hallmarks of cancers, AEG-1 plays a key functionality including progression, transformation, sustained angiogenesis, evading apoptosis, and invasion and metastasis. Clinical studies have supported that AEG-1 is actively intricated in tumor growth and progression which includes esophageal squamous cell, gastric, colorectal, hepatocellular, gallbladder, breast, prostate and non-small cell lung cancers, as well as renal cell carcinomas, melanoma, glioma, neuroblastoma and osteosarcoma. Existing studies have reported that AEG-1 expression has been induced by Ha-ras through intrication of PI3K/AKT signaling. Conversely, AEG-1 also activates PI3K/AKT pathway and modulates the defined subset of downstream target proteins via crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling cascade which further plays a crucial role in metastasis. Thus, AEG-1 may be employed as a biomarker to discern the patients of those who are likely to get aid from AEG-1-targeted medication. AEG-1 may play as an effective target to repress tumor development, occlude metastasis, and magnify the effectiveness of treatments. In this review, we focus on the molecular mechanism of AEG-1 in the process of carcinogenesis and its involvement in regulation of crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling. We also highlight the multifaceted functions, expression, clinicopathological significance and molecular inhibitors of AEG-1 in various cancer types.

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“…HCC possesses a strong ability to invade hepatic vessels (2). The molecular mechanism of hepatocarcinogenesis is complex and multi-staged, which may be related to genetic and epigenetic factors (3). HCC remains an intractable problem worldwide.…”

Section: Introductionmentioning

confidence: 99%

LncRNA HULC shRNA disinhibits miR-377-5p to suppress the growth and invasion of hepatocellular carcinoma in vitro and hepatocarcinogenesis in vivo

Cao¹,

Wei²,

Han³

et al. 2020

Ann Transl Med

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Background: Aberrant expression of up-regulated long non-coding RNA [LncRNA highly upregulated in liver cancer (HULC)] has been observed to play an important regulatory role in the development of multiple human diseases. However, the molecular mechanism underlying the role of HULC and miR-377-5p in HCC needs to be urgently explored. Methods:The mRNA and protein expression levels of HULC were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot in hepatocellular carcinoma (HCC) cell line HB611, HepG2 and H22, respectively. HULC-shRNA was transfected into HepG-2 cells, which were randomly divided into the control, shRNA-NC, and sh-HULC groups. The correlation between HULC and miR-377-5p was analyzed by performing a luciferase reporter assay. The targeting relationship between miR-377-5p and hypoxia-inhibitory factor-1α (HIF-1α) was also investigated using a luciferase reporter assay.Sh-HULC and miR-377-5p inhibitors were transfected either alone or together into HepG2 cells, and which were divided into the control group, the sh-HULC group, the miR-377-5p inhibitor, and the sh-HULC + inhibitor group for subsequent experiments. HepG2 cell proliferation and invasion were measured by 5-Ethynyl-2-Deoxyuridine (EdU) staining and Transwell invasion assay, respectively. Western plot was carried out to detect the protein expression levels of Ki67, PCNA, E-cadherin, and N-cadherin.Tumor xenograft mouse models were established to confirm the effect of HULC down-regulation on the development of HCC in vivo.Results: The mRNA and protein expression levels of HULC were markedly increased, whereas the mRNA expression levels of miR-377-5p were decreased in HCC cell lines. HepG2 cell proliferation and invasion were suppressed in the Sh-HULC group, while miR-377-5p showed the opposite. Further experiments exhibited that miR-377-5p was targeted by HULC, and an negative correlation between HULC and miR-377-5p was observed. Importantly, the in vivo experiments indicated that down-regulation of HULC could inhibit tumor growth. Taken together, our research demonstrated that down-regulation of HULC plays an anti-cancer role through restrainingHepG2 cell proliferation and invasion.Conclusions: In summary, our in vitro and in vivo findings confirmed HULC to play a role in the progression of HCC, with the underlying mechanism possibly involving the miR-377-5p/HIF-1α pathway.

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MiR-875-5p inhibits hepatocellular carcinoma cell proliferation and migration by repressing astrocyte elevated gene-1 (AEG-1) expression

Cited by 7 publications

References 0 publications

The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review

LncRNA HULC shRNA disinhibits miR-377-5p to suppress the growth and invasion of hepatocellular carcinoma in vitro and hepatocarcinogenesis in vivo

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