MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance

Du, Zhonghai; Niu, Shuxian; Xu, Xiaoyu; Xu, Qinghui

doi:10.3233/cbm-170568

Cited by 32 publications

(23 citation statements)

References 28 publications

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“…38,39 Present works have confirmed that miR-31 is downregulated in liver cancer and involved in liver cancer cell apoptosis, migration impairment, and proliferation delay. 10,40 But the underlying mechanisms remain unclear. The present study fills this gap and confirmed that miR-31 promotes HepG2 cells mitochondria-related apoptosis and inhibits proliferation and metastasis by activating the ROCK1/F-actin pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways</p>

Zhang¹,

Xu²,

Yang³

2020

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Purpose: Liver cancer is one of the most common malignant tumor in the world. miR-31 is downregulated in liver cancer and associated with tumor growth and metastasis. However, the underlying mechanism remains unclear. Methods: Cellular apoptosis was detected via MTT, TUNEL assay, LDH release and Annexin V/PI flow-cytometry analysis. Cellular migration and invasion were measured by the Transwell chamber assay. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining and mPTP opening assessment. The mitophagy activity was examined via Western blots. Results: In the present study, our results confirm that miR-31 promotes apoptosis and inhibits proliferation and metastasis in liver cancer HepG2 cells. In vitro, miR-31 promotes HepG2 cell apoptosis through the mitochondrial pathway as indicated by mitochondrial potential reduction, increased mPTP opening time, cty-c release and imbalance of pro-and anti-apoptotic proteins. Furthermore, miR-31 reduces the energy generation by inhibiting mitochondrial respiratory function. At last, it is demonstrated that miR-31 triggers the mitochondrial damage via ROCK1/F-actin pathway. Inhibiting the ROCK1/F-actin pathway abolishes the effects of miR-31 mimic on mitochondrial injury, apoptosis, proliferation arrest and migration inhibition. Conclusion: Our results reveal that miR-31 can inhibit HepG2 cell survival and metastasis by activating the ROCK1/F-actin pathway.

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Section: Discussionmentioning

confidence: 99%

<p>miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways</p>

Zhang¹,

Xu²,

Yang³

2020

OTT

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“…Therefore, the majority of patients lose the chance to undergo radical surgery, which seriously threatens patient health and quality of life (21). The prognosis of patients is poor (22). The traits of complex diseases are affected by the interaction of multiple genes.…”

Section: Discussionmentioning

confidence: 99%

Association between the expression of carbonic anhydrase�II and clinicopathological features of hepatocellular carcinoma

et al. 2019

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The present study aimed to examine the molecular marker associated with the therapy and prognosis of hepatocellular carcinoma (HCC), and further investigate the association between its expression and the clinicopathological features of HCC. To select the core genes closely associated with HCC, differentially expressed genes (DEGs) were analyzed and screened from Gene Expression Omnibus datasets (GSE 36376) using a bioinformatics approach. Tumor and adjacent tissues were collected form 112 patients of HCC who were treated by radical resection. The expression levels of carbonic anhydrase II (CA2) in the tumor and adjacent tissues were determined using reverse transcription-quantitative polymerase chain reaction analysis and immunohistochemistry. The χ 2 test was applied for observing the association between the expression of CA2 and clinicopathological features of patients with HCC. The effects of the expression of CA2 on the patients' overall survival (OS) and disease-free survival (DFS) were examined via Kaplan-Meier analysis. A total of 83 DEGs were screened and analyzed using gene network analysis, among which CA2 had direct interactions with more than one disease gene of HCC. The results of immunohistochemistry showed that CA2 was expressed at a lower level in the tumor tissues compared with the adjacent tissues (t=3.012, P=0.010). Single factor analysis revealed that the mRNA expression of CA2 was able to predict the recurrence of HCC, and was significantly associated with α-fetoprotein (AFP), microvascular invasion, tumor-node-metastasis (TNM) staging, and recurrence (P<0.05). The expression levels of AFP, CA2 and TNM staging were confirmed to be independent prognostic factors of HCC (P<0.05). Kaplan-Meier analysis demonstrated that the group with a high expression of CA2 showed increased DFS and OS, compared with the low expression group (P<0.05). These findings indicated that elevated CA2 increased DFS and OS of HCC, which suggested that CA2 may be a potential target for HCC therapy.

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“…The tumor suppressor miR-122 has been found to promote adriamycin sensitivity in HCC cells through inhibiting cell cycle, anti-apoptotic effector factors and ABC transporters [82][83][84]. Similarly, miR-31 has been found to increase the sensitivity of HCC cells to adriamycin via silencing the expression of NDRG3 [85]. In addition, down-regulated expression of tumor suppressor miRNAs, such as miR-223, miR-133a, miR-326, miR-101, miR-199a-3p, miR-215, miR-145 and miR-503, are significantly correlated with adriamycin resistance of HCC through inhibiting expression of the MDR-related genes.…”

Section: Mirnas and Resistance To Adriamycinmentioning

confidence: 99%

The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

et al. 2019

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Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumorspecific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.

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MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance

Abstract: We conclude that miR-31 is a crucial regulator in hepatocellular carcinoma, miR-31 and its target gene NDRG3 may be potential therapeutic targets for HCC treatment in the future.

Cited by 32 publications

References 28 publications

<p>miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways</p>

<p>miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways</p>

Association between the expression of carbonic anhydrase�II and clinicopathological features of hepatocellular carcinoma

The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

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