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RNA-seq in liver cancer cell and cinobufagin treatment cells

ABSTRACT: Cinobufagin, belonged to a kind of cardiotonic steroids (CSs), derived from the extracts of toad venom, which presented the significant anticancer properties as inhibitors of Na+/K+-ATPase (NKA) in many cancer cells. Nowadays, cinobufagin was usually used to apply for clinical treatments of patients in advanced stage of cancer, and improved their quality of life and prolonged their survival period. Unfortunately, long-term drug treatment had also led to multi-drug-resistance (MDR) likely other chemotherapy drugs. However, this detailed mechanism was not still clear. In the present study, we noticed that cinobufagin could trigger the protective autophagy to suppress cells apoptosis in liver cancer HepG2 and Huh-7 cells by inhibition of PI3K-AKT-mTOR pathway using RNA-seq method. We also confirmed that cinobufagin could inhibit cells proliferation and induce cells apoptosis, and generated cells autophagy by up-regulation expression of LC3B-II, Beclin 1 and Atg12-atg5. More importantly, autophagy inhibitor (MRT68921) enhances the anti-proliferation and pro-apoptosis effects of cinobufagin in HCC cells. Therefore, we thought that a combination of cinobufagin and autophagy inhibitors may be a potential effective strategy in treatment of HCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE142588 | GEO | 2019/12/26

REPOSITORIES: GEO

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Project description:Infection with antimony resistant (SbR) but not with sentitive (SbS) Leishmania donovani (LD) gives rise to aggressive pathology in mammalian hosts, the cause of which is far from clear. Some intracellular pathogens exploit autophagy for their own benefit. Here we show that induction of autophagy in normal macrophages (MF) by pharmacological mediators prior to infection with SbRLD (SbRLD-MF) enhanced their growth as compared to untreated MF, unlike SbSLD-MF. Autophagy was evident in SbRLD-MF from electron microscopical studies showing double membrane-bound compartment around amastigote. In SbRLD-MF there is induction of beclin 1, which forms the platform to recruit other interacting molecules to initiate autophagy. Knocking down the beclin 1 transcription factor Nrf2 and subsequent infection with SbRLD showed significantly lower organ parasites as compared to wild type BALB/c mice. Cessation of autophagy in SbRLD-MF at the later stage of infection is coupled with induction of miR-30a, whose binding to 3'UTR of beclin 1 leads to its post-transcriptional attenuation followed by rise in intracellular Ca++ and apoptosis. SbRLD mediated translocation of AP-1 transcription factor to the nucleus induce pri-miR-30a over-expression. Rise in Ca++ causes caspase 8 activtion leading to the cleavage of beclin 1 and initiation of apoptosis in SbRLD-MF. Apoptosis may favor parasite egress for cell to cell transmission. We also found that beclin 1 expression is present in splenocytes of kala-azar patients harbouring SbRLD but not SbSLD. Our results suggest that SbRLD has evolved a unique mechanism for its own benefit which explains, in part, the cause of aggressive pathology. Peritoneal exudate macrophages were isolated from mouse, grown in 60mm plates and infected with Leishmania donovani and total RNA was isolated from cells at 12, 18 and 24 hrs post infection. Leishmania infected macrophage miRNA expression signature was generated. Cells grown on 60mm plates and infected with Leishmania. The main objective of the microarray analysis of mmu-miRNA in antimony resistant and antimony sensitive Leishmania donovani infected macrophages are as follows: 1. To study how the expression of miRNA varies in either antimony resistant or antimony sensitive Leishmania infected macrophages as compared to the normal macrophages as a function of time. LPS was used as control. 2. To study the expression of those miRNAs which are differentially expressed in antimony resistant and antimony sensitive Leishmania infected macrophages at each time point post infection. 3. To identify those miRNAs which are responsible for degradation of autophagy initiating protein beclin 1 mRNA

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RNA-seq in liver cancer cell and cinobufagin treatment cells

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