Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4

Fujisawa, Koichi; Terai, Shuji; Takami, Taro; Yamamoto, Naoki; Yamasaki, Takahiro; Matsumoto, Toshihiko; Yamaguchi, Kazuhito; Owada, Yuji; Nishina, Hiroshi; Noma, Takafumi; Sakaida, Isao

doi:10.1186/s13046-016-0322-2

Cited by 47 publications

(57 citation statements)

References 39 publications

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“…We thus predicted the targets of miR-199a-3p using the following websites: TargetScan ( http://www.targetscan.org/ ), miRDB ( http://mirdb.org/miRDB/ ). Among them, we choose the AK4 gene as our target, which was previously found to be related to cancer drug resistance [ 25 ]. To further check the effect of the AK4 gene, we tested its expression at both mRNA and protein levels in the above OS cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…AK4 was reported to be involved in the development of cancers, and is used as a potential therapeutic target for anticancer treatment. For example, the AK4 expression level could modulate the anti-cancer drug sensitivity through regulating mitochondrial activity [ 25 ]. Of note, a previous study found that AK4 promotes the metastasis of lung cancers by downregulating the transcription factor ATF3 [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

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MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4

et al. 2018

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BackgroundMicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer.MethodsWe performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug resistance using drug resistance profiling assays. We further predicted the putative signal pathway involved in the miR-199a-3p-mediated OS drug-resistance.ResultsThe AK4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance. In addition, the activity of the NF-кB signaling pathway was drastically altered by the forced changes of the miR-199a-3p level in OS cells.ConclusionsOur data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the OS drug resistance.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4460-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4

et al. 2018

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“…We first predicted the targets of miR-199a-3p using the following websites: Targetscan and miRDB. Among them, we choose the AK4 gene as our target, which was previously found to be related to cancer drug resistance [ 26 , 27 ]. We then detected the expression levels of miR-199a-3p and AK4 in the radiosensitive and radioresistant cell lines.…”

Section: Resultsmentioning

confidence: 99%

The miR-199a-3p regulates the radioresistance of esophageal cancer cells via targeting the AK4 gene

et al. 2018

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BackgroundMiRNAs was recognized as vital regulators involved in cancer development. Radioresistance remains a major obstacle for effective treatment of cancers. The mechanisms on the miRNA-mediated radioresistance of cancers are still poorly understood. The main subject of this study is to find new miRNA biomarker that regulates the radioresistance of esophageal cancer (EC).MethodsThe cumulative dose of radiation assays were used to screen the EC radioresistant cell lines. Wound-healing and invasion assays were used to characterize the properties of these cell lines. The following survival fraction experiments were performed to test the effects of miR-199a-3p and AK4 in the radioresistance of EC. In addition, we used the luciferase reporter assays to identify the putative underlying mechanism that relates to the miR-199a-3p regulated radio-resistance.ResultsWe found that the AK4 gene is one of the targets of miR-199a-3p, which promotes the radioresistance of EC cells. The following experiments by force reversal of the miR-199a-3p or AK4 levels confirmed the relationship of miR-199a-3p and AK4 with the radioresistance of EC cells. In addition, the activities of several signaling pathway were drastically altered by the forced changes of the miR-199a-3p level in EC cells.ConclusionTaken together, we found that miR-199a-3p can be potentially used as a biomarker for the EC radioresistance. Moreover, these results provides new insights into the mechanism on the radioresistance of EC cells, and also might guide the clinical therapy of EC.

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“…Previous studies have also confirmed that AK4 played a role in cancer development. AK4 could modulate anticancer drug sensitivity in lung cancer via the regulation of mitochondrial activity ( 28 ). AK4 could also affect multi-chemoresistance and radioresistance in osteosarcoma and esophageal cancer, and AK4 expression was regulated by miR-199a-3p ( 21 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of AK4 as a novel therapeutic target for serous ovarian cancer

et al. 2020

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The present study aimed to assess the expression level of adenylate kinase 4 (AK4) in human serous ovarian cancer (SOC) tissues and investigate the possible involvement of AK4 in SOC progression. Bioinformatics analysis based on The Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) assays were performed to assess the expression level of AK4 in human SOC tissues. Clinical pathological features of patients with SOC were also evaluated. Colony formation, MTT, wound healing and Transwell assays were conducted to investigate the effects of AK4 on the proliferation, migration, and invasion of SOC cells in vitro . Mouse xenograft and lung metastasis models were developed to evaluate the effects of AK4 on tumor growth and metastasis in vivo . High expression levels of AK4 were identified in human SOC tissues compared with in normal tissues according to TCGA database and the results of IHC assays. A contribution of AK4 to tumor growth and metastasis of SOC cells in vivo was also shown. The present study confirmed the involvement of AK4 in the progression of SOC, and the results indicated that AK4 could serve as a novel therapeutic target for SOC treatment.

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Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4

Cited by 47 publications

References 39 publications

MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4

MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4

The miR-199a-3p regulates the radioresistance of esophageal cancer cells via targeting the AK4 gene

Identification of AK4 as a novel therapeutic target for serous ovarian cancer

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