METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy

Xin, Lin; Zhou, Qi; Yuan, Yi‐Wu; Zhou, Liqiang; Liu, Li; Li, Shihao; Liu, Chuan

doi:10.1007/s00432-019-03015-w

Cited by 66 publications

(44 citation statements)

References 22 publications

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“…Briefly, HULC promotes cell proliferation of different kinds of tumor cells. 25,28,29 For instance, overexpression of HULC promotes cell proliferation in lung cancer by upregulating sphingosine kinase 1. 19 In contrast, knockdown of HULC resulted in the decreased proliferation of both osteosarcoma and hepatocellular carcinoma cancer cells.…”

Section: Discussionmentioning

confidence: 99%

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

Cai

Yang

Sun

et al. 2020

CMAR

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Background: LncRNA PTCSC3 (PTCSC3) inhibits thyroid cancer cervical carcinoma and glioma, while its roles in gastric cancer are unknown. Studies have reported that HULC could serve as a potential biomarker for the diagnosis and prognosis of gastric cancer (GC). Our study aimed to investigate the potential interaction between PTCSC3 and HULC in gastric cancer. Methods: This study enrolled 77 gastric cancer patients at the First Affiliated Hospital of Anhui Medical University from January 2016 to January 2018. RT-qPCR was performed to analyze gene expression levels. Cell transfections were carried out to evaluate gene interactions. Transwell assays and wound healing assays were used to analyze the effects of transfection on cell invasion and migration. Western blotting was also used to illustrate the possibility that lncRNA PTCSC3 and lncRNA HULC negatively affected each other through WNT signal path. Results: We showed that PTCSC3 was downregulated in tumor tissues of gastric cancer patients in comparison to that in adjacent healthy tissues, and an inverse correlation between the expression levels of PTCSC3 and AJCC stage was observed. LncRNA HULC (HULC) was upregulated in tumor and inversely correlated with PTCSC3 in tumor tissues. Overexpression of PTCSC3 mediated the inhibition of HULC, while overexpression of HULC also mediated the inhibition of PTCSC3. PTCSC3 inhibited, while HULC promoted invasion and migration of gastric cancer cells. In addition, overexpression of HULC attenuated the effects of overexpression of PTCSC3. However, overexpression of PTCSC3 showed no significant effects on cell proliferation. We also found that PTCSC3/HULC affected each other to regulate cell invasion and migration through the Wnt/β-catenin signaling. Conclusion: Therefore, overexpression of PTCSC3 inhibited the invasion and migration of gastric cancer cells, and the function of PTCSC3 is associated with HULC.

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Section: Discussionmentioning

confidence: 99%

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

Cai

Yang

Sun

et al. 2020

CMAR

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“…Drug resistance of cancer cells is one of the major causes of chemotherapy failure [22]. LncRNAs are reported to induce the drug resistance by regulating drug metabolism, autophagy, apoptosis and epithelial-mesenchymal transition [23][24][25][26]. We previously elucidated that lncRNA UCA1 promotes tumor development and metastasis in GC [18,27].…”

Section: Discussionmentioning

confidence: 99%

LncRNA UCA1 promotes cisplatin resistance in gastric cancer via recruiting EZH2 and activating PI3K/AKT pathway

et al. 2020

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Background: Drug resistance of cancer cells is one of the major causes of chemotherapy failure. Recently research demonstrated that long non-coding RNA Urothelial cancer associated 1 (UCA1) could promote tumor cisplatin resistance. In this study, we aim to investigate the role of UCA1 in the cisplatin treatment of gastric cancer and its underlying mechanism. Methods: Cell counting kit-8 (CCK-8) assay and apoptosis assay were used to detect the effects of different doses of cisplatin on the proliferation and apoptosis of gastric cancer. We examined the expression relationship between the Enhancer of Zeste Homologue 2 (EZH2) and UCA1 by quantitative Real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Western blot analysis was also performed to detect the expression levels of apoptosis-related proteins, EZH2 and key genes in PI3K/AKT signaling pathway, RIP and RNA pull down assays were performed to explore the interaction between UCA1 and EZH2. Results: We demonstrated that higher the UCA1 expression levels in GC tissues correlated with the poorer the prognosis of patients according to the TCGA database, the GEO database. Moreover, overexpression of UCA1 promotes GC cell proliferation and inhibits cisplatin-induced apoptosis. Knockdown of UCA1 showed the opposite results. Besides, UCA1 exerted its function through interacting with EZH2 and regulates EZH2 expression, knockdown of EZH2 decreased cisplatin resistance of GC cells. Hence, UCA1 promotes cisplatin resistance of GC via recruiting EZH2 and activating PI3K/AKT pathway. Conclusion: Our research revealed the lncRNA UCA1 promoted the cisplatin resistance of GC by recruiting EZH2 and activating PI3K/AKT pathway to modulate cell apoptosis, indicating treatments targeting UCA1 or EZH2 might provide meaningful therapeutic strategies for cisplatin-resistance GC patients.

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“…After that, the CR-GC cells were subjected to cisplatin (20 μg/ml) combined with low-dose DB (12.5 μM) for 0 h, 24 h, 48 h and 72 h, respectively. To induce the acquired cisplatin-resistant GC (ACR-GC) cells, the parental CS-GC cells were exposed to continuous low-dose cisplatin (from 0.5 μg/ml to 5 μg/ml, for 80 days) in a step-wise manner based on the experimental procedures provided by the previous publications [9,10].…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…The CR-GC cells were prepared, and a commercial TRIzol reagent (Invitrogen, USA) was obtained to extract the total RNA from the cells in keeping with the producer's protocol. After that, the Real-Time qPCR kit (Invitrogen, USA) was employed to to examine the mRNA levels of PD-L1, SOX2, OCT4, Nanog and βactin in the CR-GC cells according to the experimental procedures provided by the previous publications [9,10]. The primer sequences for Real-Time qPCR were included in the Table 2.…”

Section: Real-time Qpcrmentioning

confidence: 99%

“…We bought the RIPA lysis buffer (Beyotime, Shanghai, China) to extract the total protein from CR-GC cells and mice tumor tissues based on the experimental procedures provided by the manufacturer. After that, the protein levels of Cyclin D1, CDK2, β-actin, PD-L1, SOX2, OCT4, Nanog, NLRP3, ASC, IL-1β, IL-18, cleaved Caspase-3 (p17) and Bax were determined by using the Western Blot analysis, and the experimental procedures had been well documented in the previous publications [9,10]. Besides, the detailed information for the involved primary antibodies were documented in the Table 3.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Low-dose Diosbulbin-B (DB) Regulates Tumor-Intrinsic PD-L1/NLRP3 Signaling Pathway to Increase Cisplatin-Sensitivity in Gastric Cancer (GC)

Qiu

Xue

2020

Preprint

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Background: Generation of cisplatin (DDP)-resistance by gastric cancer (GC) cells seriously limits the therapeutic efficacy of this drug in clinic, and recent data suggested that Diosbulbin-B (DB), the main anti-tumor compound of Dioscorea bulbifera L, was effective to improve cisplatin-sensitivity in GC cells. However, the underlying mechanisms are still largely unknown.Methods: Genes expressions were determined by Real-Time qPCR and Western Blot. Cell viability was evaluated by cell counting kit-8 and trypan blue staining assay. Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The Spheroid formation assay was used to evaluated cell stemness. Immunohistochemistry (IHC) was employed to examine the expressions and localization of Ki67 protein in mice tumor tissues.Results: Here we found that low-dose DB (12.5 μM) downregulated PD-L1 to activate NLRP3-medicated pyroptosis, and inhibited cancer stem cells (CSCs) properties, to sensitize cisplatin-resistant GC (CR-GC) cells to cisplatin. Mechanistically, the CR-GC cells were obtained, and either low-dose DB or cisplatin alone had little effects on cell viability in CR-GC cells, while low-dose DB significantly induced apoptotic cell death in cisplatin treated CR-GC cells. In addition, low-dose DB triggered cell pyroptosis in CR-GC cells stimulated with cisplatin, which were abrogated by silencing NLRP3. Next, CSCs tended to be enriched in CR-GC cells, instead of their parental cisplatin-sensitive GC (CS-GC) cells, and low-dose DB (12.5 μM) inhibited spheroid formation and stemness biomarkers (CD44, CD133, SOX2, OCT4 and Nanog) expressions to eliminate CSCs in CR-GC cells, which were reversed by upregulating programmed death ligand-1 (PD-L1). Furthermore, we proved that PD-L1 negatively regulated NLRP3 in CR-GC cells, and low-dose DB (12.5 μM) activated NLRP3-mediated pyroptotic cell death in cisplatin treated CR-GC cells by downregulating PD-L1. Also, low-dose DB aggravated the inhibiting effects of cisplatin on tumorigenesis of CR-GC cells in vivo. Conclusions: Collectively, low-dose DB (12.5 μM) regulated intrinsic PD-L1/NLRP3 pathway to improve cisplatin-sensitivity in CR-GC cells, and this study provided alternative therapy treatments for GC.

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METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy

Cited by 66 publications

References 22 publications

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

LncRNA UCA1 promotes cisplatin resistance in gastric cancer via recruiting EZH2 and activating PI3K/AKT pathway

Low-dose Diosbulbin-B (DB) Regulates Tumor-Intrinsic PD-L1/NLRP3 Signaling Pathway to Increase Cisplatin-Sensitivity in Gastric Cancer (GC)

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