LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes

Abstract

Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues. Overexpression of HOTAIR enhanced gastric cancer cell proliferation, promoted cell cycle G1/S transition, but decreased tumor cell apoptosis. Furthermore, HOTAIR was shown to directly bind to and inhibit miR-126 expression and then to promote VEGFA and PIK3R2 expression and activate the PI3K/AKT/MRP1 pathway. In conclusion, the data demonstrated that high HOTAIR expression acted as a competitive endogenous RNA to promote cisplatin resistance in gastric cancer. Further study will evaluate HOTAIR expression as a biomarker to predict treatment response of cisplatin and explore inhibition of HOTAIR expression as a novel strategy for anti-cisplatin resistance in human gastric cancer.

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Effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition

Abstract

This study examined the effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition. Different CoCl₂ concentrations were used to treat A549 cells and establish a CoCl₂-induced hypoxic model of A549 cells. MTT and clone formation assays were used to determine the effects of different concentrations of CoCl₂ on the growth and proliferation of A549 cells treated by different doses of X-ray irradiation. The siRNA-expressing vector was transfected by liposomes and for silencing of TUSC3. Flow cytometry was used to measure cell cycle changes and apoptosis rate. Real-time quantitative polymerase chain reaction (qRT-PCR) assay was performed to detect the expression of TUSC3 mRNA. Western blotting was applied to detect the changes of TUSC3, LC3, and p62 proteins under different CoCl₂ concentrations and after siRNA silencing of TUSC3. The TUSC3 levels in A549 cells increased under hypoxic conditions in a dose-dependent manner (P < 0.05). Hypoxia inhibited the growth and proliferation of A549 cells and promoted apoptosis (P < 0.05). With an increasing dose of X-ray irradiation, A549 cells showed significantly increased growth and proliferation and decreased apoptosis (P < 0.05). After siRNA-TUSC3 was transfected by liposome, the TUSC3 level was substantially inhibited (P < 0.05). Silencing TUSC3 inhibited A549 cell growth and proliferation after radiotherapy under hypoxic condition, promoted apoptosis, increased G0/G1 phase cells, and reduced S phase cells (all P < 0.05). Hypoxia and radiation along with different CoCl₂ concentrations could induce cell autophagy, which increased with concentration and dose, while silencing the TUSC3 gene inhibited autophagy (all P < 0.05). RNAi silencing of TUSC3 inhibited growth and proliferation, while enhanced apoptosis and radiation sensitivity of hypoxic A549 lung adenocarcinoma cells.

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LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes

Abstract

Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues. Overexpression of HOTAIR enhanced gastric cancer cell proliferation, promoted cell cycle G1/S transition, but decreased tumor cell apoptosis. Furthermore, HOTAIR was shown to directly bind to and inhibit miR-126 expression and then to promote VEGFA and PIK3R2 expression and activate the PI3K/AKT/MRP1 pathway. In conclusion, the data demonstrated that high HOTAIR expression acted as a competitive endogenous RNA to promote cisplatin resistance in gastric cancer. Further study will evaluate HOTAIR expression as a biomarker to predict treatment response of cisplatin and explore inhibition of HOTAIR expression as a novel strategy for anti-cisplatin resistance in human gastric cancer.

http://ift.tt/2g5gROW

Effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition

Abstract

This study examined the effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition. Different CoCl₂ concentrations were used to treat A549 cells and establish a CoCl₂-induced hypoxic model of A549 cells. MTT and clone formation assays were used to determine the effects of different concentrations of CoCl₂ on the growth and proliferation of A549 cells treated by different doses of X-ray irradiation. The siRNA-expressing vector was transfected by liposomes and for silencing of TUSC3. Flow cytometry was used to measure cell cycle changes and apoptosis rate. Real-time quantitative polymerase chain reaction (qRT-PCR) assay was performed to detect the expression of TUSC3 mRNA. Western blotting was applied to detect the changes of TUSC3, LC3, and p62 proteins under different CoCl₂ concentrations and after siRNA silencing of TUSC3. The TUSC3 levels in A549 cells increased under hypoxic conditions in a dose-dependent manner (P < 0.05). Hypoxia inhibited the growth and proliferation of A549 cells and promoted apoptosis (P < 0.05). With an increasing dose of X-ray irradiation, A549 cells showed significantly increased growth and proliferation and decreased apoptosis (P < 0.05). After siRNA-TUSC3 was transfected by liposome, the TUSC3 level was substantially inhibited (P < 0.05). Silencing TUSC3 inhibited A549 cell growth and proliferation after radiotherapy under hypoxic condition, promoted apoptosis, increased G0/G1 phase cells, and reduced S phase cells (all P < 0.05). Hypoxia and radiation along with different CoCl₂ concentrations could induce cell autophagy, which increased with concentration and dose, while silencing the TUSC3 gene inhibited autophagy (all P < 0.05). RNAi silencing of TUSC3 inhibited growth and proliferation, while enhanced apoptosis and radiation sensitivity of hypoxic A549 lung adenocarcinoma cells.

http://ift.tt/2fCGo5C

Effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition

Abstract

This study examined the effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition. Different CoCl₂ concentrations were used to treat A549 cells and establish a CoCl₂-induced hypoxic model of A549 cells. MTT and clone formation assays were used to determine the effects of different concentrations of CoCl₂ on the growth and proliferation of A549 cells treated by different doses of X-ray irradiation. The siRNA-expressing vector was transfected by liposomes and for silencing of TUSC3. Flow cytometry was used to measure cell cycle changes and apoptosis rate. Real-time quantitative polymerase chain reaction (qRT-PCR) assay was performed to detect the expression of TUSC3 mRNA. Western blotting was applied to detect the changes of TUSC3, LC3, and p62 proteins under different CoCl₂ concentrations and after siRNA silencing of TUSC3. The TUSC3 levels in A549 cells increased under hypoxic conditions in a dose-dependent manner (P < 0.05). Hypoxia inhibited the growth and proliferation of A549 cells and promoted apoptosis (P < 0.05). With an increasing dose of X-ray irradiation, A549 cells showed significantly increased growth and proliferation and decreased apoptosis (P < 0.05). After siRNA-TUSC3 was transfected by liposome, the TUSC3 level was substantially inhibited (P < 0.05). Silencing TUSC3 inhibited A549 cell growth and proliferation after radiotherapy under hypoxic condition, promoted apoptosis, increased G0/G1 phase cells, and reduced S phase cells (all P < 0.05). Hypoxia and radiation along with different CoCl₂ concentrations could induce cell autophagy, which increased with concentration and dose, while silencing the TUSC3 gene inhibited autophagy (all P < 0.05). RNAi silencing of TUSC3 inhibited growth and proliferation, while enhanced apoptosis and radiation sensitivity of hypoxic A549 lung adenocarcinoma cells.

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The role of viral protein Ac34 in nuclear relocation of subunits of the actin-related protein 2/3 complex

Abstract

The actin nucleator actin-related protein complex (Arp2/3) is composed of seven subunits: Arp2, Arp3, p40/ARPC1 (P40), p34/ARPC2 (P34), p21/ARPC3 (P21), p20/ARPC4 (P20), and p16/ARPC5 (P16). Arp2/3 plays crucial roles in a variety of cellular activities through regulation of actin polymerization. Autographa californica multiple nucleopolyhedrovirus (AcMNPV), one of the best-studied alphabaculoviruses, induces Arp2/3 nuclear relocation and mediates nuclear actin polymerization to assist in virus replication. We have demonstrated that Ac34, a viral late-gene product, induces translocation of the P40 subunit of Arp2/3 to the nucleus during AcMNPV infection. However, it remains unknown whether Ac34 could relocate other Arp2/3 subunits to the nucleus. In this study, the effects of the viral protein Ac34 on the distribution of these subunits were studied by an immunofluorescence assay. Arp2, P34, P21, and P20 cloned from Spodoptera frugiperda (Sf9) cells showed mainly cytoplasmic localization and were relocated to the nucleus in the presence of Ac34. In addition, Arp3 was localized in the cytoplasm in both the presence and absence of Ac34, and P16 showed whole-cell localization. In contrast to Sf9 cells, all subunits of mammalian Arp2/3 showed no nuclear relocation in the presence of Ac34. Co-immunoprecipitation analysis of the interaction between Ac34 and Arp2/3 subunits revealed that Ac34 bound to P40, P34, and P20 of Sf9 cells. However, none of the subunits of mammalian Arp2/3 interacted with Ac34, indicating that protein-protein interaction is essential for Ac34 to relocate Arp2/3 subunits to the nucleus.

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Primary EBV infection and hypersensitivity to mosquito bites: a case report

Abstract

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