Overexpression of RBM5 induces autophagy in human lung adenocarcinoma cells

Su, Zheng; Wang, Ke; Li, Ranwei; Yin, Jinzhi; Hao, Yuqiu; Lv, Xuejiao; Li, Junyao; Zhao, Lijing; Du, Yanwei; Li, Ping; Zhang, Jie

doi:10.1186/s12957-016-0815-7

Cited by 16 publications

(14 citation statements)

References 60 publications

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“…It is important to note that RBM5 expression was recently shown to increase autophagy levels in a NSCLC cell line (Su et al, 2016), therefore, we also examined the expression of autophagy markers BCL2 , NF-κB , LC-3 , LAMP1 and BECLIN1 in the RNA-Seq data from our cisplatin-treated C4 cells. Only NF-κB, however, was significantly differentially expressed compared to control; thus, autophagy does not seem to be a mechanism by which RBM5 expression influences membrane integrity in cisplatin-treated SCLC cells.…”

Section: Resultsmentioning

confidence: 99%

RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways

Loiselle

Roy

Sutherland

2016

Heliyon

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Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, with almost 95% of patients succumbing to the disease. Although RBM5, a tumor suppressor gene, is downregulated in the majority of lung cancers, its role in SCLC is unknown. Using the GLC20 SCLC cell line, which has a homozygous deletion encompassing the RBM5 gene locus, we established stable RBM5 expressing sublines and investigated the effects of RBM5 re-expression. Transcriptome and target identification studies determined that RBM5 directly regulates the cell cycle and apoptosis in SCLC cells, as well as significantly downregulates other important transformation-associated pathways such as angiogenesis and cell adhesion. RNA sequencing of paired non-tumor and tumor SCLC patient specimens showed decreased RBM5 expression in the tumors, and expression alterations in the majority of the same pathways that were altered in the GLC20 cells and sublines. Functional studies confirmed RBM5 expression slows SCLC cell line growth, and increases sensitivity to the chemotherapy drug cisplatin. Overall, our work demonstrates the importance of RBM5 expression to the non-transformed state of lung cells and the consequences of its deletion to SCLC development and progression.

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Section: Resultsmentioning

confidence: 99%

RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways

Loiselle

Roy

Sutherland

2016

Heliyon

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“…Besides the above two mechanisms, other signaling may be also involved in the anti-tumor role of RBM5. For example, RBM5 was also shown to downregulate EGFR expression and induce cell autophagy [20, 21]. Autophagy is another autonomic programmed cell death or type II PCD.…”

Section: Discussionmentioning

confidence: 99%

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/β-catenin signaling and induction of apoptosis

et al. 2017

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BackgroundGliomas are one of the most common malignant brain tumors and bring a big threat to human life as traditional therapy is unsatisfactory. RBM5 was a RNA-binding motif protein and was reported as a tumor suppressor. But the role of RBM5 in gliomas was unknown.MethodsThe mRNA level of RBM5 was determined in gliomas tissues and cell lines by real-time quantitative PCR (qRT-PCR) assay while the association of RBM5 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. Lentivirus was used to overexpress RBM5 in gliomas cells. MTT and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis when the ability of cell migration and invasion was analyzed by transwell assay with/without Matrigel. Cell apoptosis rate was determined with fluorescence-activated cell sorting (FACS) method. Then, expression of apoptosis molecules and critical members in Wnt/β-catenin pathway were detected by western blot analysis.ResultsRBM5 was shown to be downregulated in gliomas tissues and gliomas cell lines. And decreased RBM5 expression was clinically correlated with tumor stage, patient age, and poor prognosis of gliomas patients. The proliferation and DNA synthesis was dramatically inhibited when RBM5 was overexpressed in SHG44 or U251 cells. Also, the ability of cell migration and invasion was disrupted. Then, the level of β-catenin and Cyclin D1 significantly decreased when DKK1 and P-GSK-3β increased reversely in SHG44 cells, which suggested that RBM5 inhibited canonical Wnt/β-catenin signaling. Meanwhile, we demonstrated that caspase3-mediated apoptotic pathway was activated by RBM5 as Bax, TNF-α, and cleaved caspase3 were greatly upregulated while antiapoptotic molecule Bcl-2 was downregulated. Additionally, that apoptotic rate increased significantly from less than 1 to 32% in RBM5-overexpressed SHG44 cells further supported the pro-apoptosis role of RBM5 in gliomas cells.ConclusionsRBM5 plays a suppressor role in human gliomas by inhibiting Wnt/β-catenin signaling and inducing cell apoptosis. This study improves our knowledge about the carcinogenesis and progression of human gliomas, which would greatly contribute to the therapy for gliomas patients.

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“…PC12 cells (5 × 10 4 /well) were incubated with MDC (50 μM) in a 96-well plate with serum-free medium at 37 °C for 30 min in the dark. After incubation, cells were washed four times with cold PBS, and fluorescent micrographs were obtained with a Cell Analyzer 2000 52 .…”

Section: Methodsmentioning

confidence: 99%

Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells

Zhao

et al. 2018

Sci Rep

145

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Neurodegenerative diseases (NDD) are typically associated with neuron loss in nervous system areas. Interventions with related death mechanisms may ameliorate NDD progression. Oxidative stress plays an important role in NDD cell death routines. However, tert-butylhydroperoxide (t-BHP), a widely used oxidative stress stimulus, induces neural cell death through a mechanism that remains elusive. In our study, the ferroptosis marker events occurred after co-treatment with 100 μM t-BHP for 1 h, all of which were reversed in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine, implying the occurrence of ferroptosis. Moreover, mitochondrial dysfunction accompanied by a decreased in membrane potential and ATP production, increased mitochondrial ROS generation. Furthermore, this mitochondrial dysfunction could be reversed by Fer-1. In addition, JNK1/2 and ERK1/2 were activated upstream of the ferroptosis and mitochondrial dysfunction. In summary, these data suggest that ferroptosis, coupled with mitochondrial dysfunction, was involved in t-BHP-induced PC12 death. JNK1/2 and ERK1/2 played important roles in t-BHP-induced cell death. Overall, this study might provide clues to the oxidative stress-based strategies for cell protection in NDD.

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Overexpression of RBM5 induces autophagy in human lung adenocarcinoma cells

Cited by 16 publications

References 60 publications

RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways

RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/β-catenin signaling and induction of apoptosis

Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells

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