APRIL Induces Cisplatin Resistance in Gastric Cancer Cells via Activation of the NF-κB Pathway

Zhi, Xiaofei; Tao, Jinqiu; Xiang, Guoliang; Cao, Hongxin; Liu, Zijun; Yang, Kun-Xing; Lv, Chengyu; Ni, Shaozhong

doi:10.1159/000369720

Cited by 31 publications

(22 citation statements)

References 40 publications

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“…Although APRIL has low or no expression in various normal cells, previous studies have shown that it is overexpressed in many malignancies, such as colorectal cancer [13], pancreatic cancer [26], and gastric cancer [27], suggesting that APRIL plays an important role in the carcinogenesis of these tumors. Moreover, APRIL also owns an ability to stimulate tumor cell proliferation and survival in vitro and in vivo by interaction with the intracellular environment.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, it may enable deeper insight into the regulation of gene expression and the potential complexity in HCC. Besides, although it was reported that APRIL could promote tumor progression via, for example, TGF-β1/ERK, PI3K/Akt, and NF-κB signaling pathways [13,27,31], further studies are also needed to elucidate the specific mechanisms of miR-383-APRIL axis in hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

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miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL

Chen¹,

Guan²,

Gu³

et al. 2015

Tumor Biol.

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Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL

Chen¹,

Guan²,

Gu³

et al. 2015

Tumor Biol.

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“…A previous study revealed that APRIL could upregulate the activity of nuclear factor NF-κB (22). Therefore, we speculated that APRIL knockdown and/or JXY treatment may downregulate the activity of nuclear factor NF-κB directly.…”

Section: Resultsmentioning

confidence: 99%

Synergisic effect of APRIL knockdown and Jiedu Xiaozheng Yin, a Chinese medicinal recipe, on the inhibition of hepatocellular carcinoma cell proliferation

et al. 2016

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It is well documented that A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily, plays a crucial role in the occurrence and development of tumors. In the present study, we evaluated the synergistic effect of APRIL knockdown and Jiedu Xiaozheng Yin (JXY), a Traditional Chinese Medicinal recipe, on the inhibition of hepatocellular carcinoma (HCC) cell proliferation and elucidated the underlying mechanism. The results demonstrated that both APRIL knockdown using small interfering RNA (siRNA) and JXY treatment could trigger cell cycle arrest and cell apoptosis, and suppress HCC cell proliferation through an NF-κB-related pathway. Synergism was further demonstrated between APRIL knockdown and JXY treatment. In conclusion, these results indicate that APRIL is a target gene for HCC and combination of siRNA-APRIL and JXY application holds great promise as a novel approach for the treatment of APRIL-positive HCC.

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“…DDP, a chemotherapy drug commonly used to treat gastric cancer [20–22] acts by inducing mitochondrial apoptosis in cancer cells; however, drug-resistant gastric cancer cells are not sensitive to this agent, and thus, considerable attention has been placed on this issue [23, 24]. Studies have indicated that TCM combination with chemotherapy for cancer can enhance the efficacy of and diminish the side effects and complications caused by chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

The Zuo Jin Wan Formula Induces Mitochondrial Apoptosis of Cisplatin‐Resistant Gastric Cancer Cells via Cofilin‐1

Tang

Sun

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy. Here we found that phosphorylated cofilin-1 (p-cofilin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines (SGC7901 and BGC823), and that DDP induced the dephosphorylation of p-cofilin-1 in both parent lines but not in the DDP-resistant lines. However, we noted that the traditional Chinese medicine formula Zuo Jin Wan (ZJW) could induce the dephosphorylation of p-cofilin-1 and promote cofilin-1 translocation from the cytoplasm into the mitochondria in both SGC7901/DDP and BGC823/DDP cells. This mitochondrial translocation of cofilin-1 was found to induce the conversion of filamentous actin to globular-actin, activate mitochondrial damage and calcium overloading, and induce the mitochondrial apoptosis pathway. We further observed that these effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with cofilin-1-specific siRNA, or treatment with a PP1 and PP2A inhibitor. These results suggest that ZJW is an effective drug therapy for patients with DDP-resistant gastric cancer.

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APRIL Induces Cisplatin Resistance in Gastric Cancer Cells via Activation of the NF-κB Pathway

Cited by 31 publications

References 40 publications

miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL

miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL

Synergisic effect of APRIL knockdown and Jiedu Xiaozheng Yin, a Chinese medicinal recipe, on the inhibition of hepatocellular carcinoma cell proliferation

The Zuo Jin Wan Formula Induces Mitochondrial Apoptosis of Cisplatin‐Resistant Gastric Cancer Cells via Cofilin‐1

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