MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways

Xu, Yan; Huang, Ji; Ma, Leina; Shan, Juanjuan; Shen, Junjie; Yang, Zhi; Liu, Limei; Luo, Yongli; Yao, Chao; Qian, Cheng

doi:10.1016/j.canlet.2015.11.034

Cited by 146 publications

(133 citation statements)

References 42 publications

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“…Meanwhile, the MAPK signaling pathway is a major target of sorafenib therapy. However, several studies have also clearly indicated that activation of the MAPK cascade is associated with drug resistance (21)(22)(23). Concomitant with the present study, overexpression of p-Akt and p-ERK1/2 results in sorafenib resistance (24).…”

Section: Discussionmentioning

confidence: 51%

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

Zhang

Wang

et al. 2018

Oncol Lett

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Abstract. Long-term sorafenib treatment triggers resistance to chemotherapy in patients with hepatocellular carcinoma (HCC). In order to investigate the mechanisms of sorafenib resistance in HCC, the aim of the present study was to develop a resistant human liver cell line via long-term exposure to sorafenib. The cytotoxicity cell counting kit-8 assay was used to evaluate drug sensitivity. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine the molecular mechanisms underpinning sorafenib resistance. Migratory and invasive properties in resistant cells were assessed using Transwell assays. The results from the present study revealed that resistant cells became insensitive to sorafenib treatment and exhibited increased migratory and invasive capacities. Activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway and epithelial-mesenchymal transition was characteristic of resistant cells. The use of LY294002, a PI3K inhibitor, was able to suppress the activation of Akt and extracellular signal-regulated kinase 1/2, attenuated the migratory and invasive capacities of resistant cells. Data from the present study indicates that inhibition of the PI3K signaling pathway with LY294002 exerts suppressive effects on sorafenib resistance and provides an attractive novel therapeutic regime in patients with advanced HCC.

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Section: Discussionmentioning

confidence: 51%

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

Zhang

Wang

et al. 2018

Oncol Lett

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“…This ncRNA was significantly reduced in sorafenib-resistant HCC cells. Xu et al demonstrated that miR-122 restoration increases sensitivity to sorafenib and induces apoptosis by repressing IGF1R (326). miR-122 is also involved in the control of arginine transport by targeting the solute carrier family 7 (SLC7).…”

Section: Drugs/non-coding Rnas Subnetworkmentioning

confidence: 99%

The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients. For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity. This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms. We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach. Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs. Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups. We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments.

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“…Reports show that miR-17-92 cluster, miR-1180, miR-107, and miR-25 are consistently up-regulated in primary HCC tissues [6][7][8][9]. MiR-192, miR-122, miR-34a, and miR-149 are commonly down-regulated in HCC [10][11][12][13]. Some miRNAs targeting signaling pathways including Wnt/b-catenin, Ras, TGF-b, and JAK/STAT regulate HCC progression [2][3][4][5].…”

Section: Introductionmentioning

confidence: 96%

Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting ZEB2

Jiang

Wen

Deng

et al. 2017

Biomedicine & Pharmacotherapy

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MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways

Cited by 146 publications

References 42 publications

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

Inhibition of the PI3K/Akt signaling pathway reverses sorafenib‑derived chemo‑resistance in hepatocellular carcinoma

The Network of Non-coding RNAs in Cancer Drug Resistance

Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting ZEB2

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