Background: Long non-coding RNAs (lncRNAs) play pivotal roles in carcinogenesis and the development of drug resistance in various malignancies. Objectives: The current study aimed to explore the impact of antisense non-coding RNA in the INK4 locus (ANRIL) silencing on proliferation and the sensitivity of KATO III gastric cells to the doxorubicin as a common chemotherapeutic agent. Methods: The KATO III cells were transfected with ANRIL siRNA (si-ANRIL) using Lipofectamine™2000 reagent. Following that, the relative ANRIL levels were determined by quantitative Real-Time PCR. Trypan blue assay was conducted to observe the tumor cell proliferation following the transfection. Moreover, the MTT assay was performed to identify the cytotoxic effects of doxorubicin and si-ANRIL alone or in combination on KATO III cells. The effects of si-ANRIL/doxorubicin on KATO III cells migration and apoptosis were assessed by wound healing assay and ELISA cell death method, respectively. Results: The results showed that the si-ANRIL significantly diminished ANRIL expression level in a time-dependent manner contributing to the distinct repression of cell growth and enhanced apoptosis. Furthermore, the si-ANRIL synergistically elevated the cytotoxic impacts of doxorubicin. Additionally, the ANRIL down-regulation dramatically promoted its induction of apoptosis. Moreover, KATO III cells transfected with si-ANRIL and exposed with doxorubicin revealed significantly reduced invasion capability and enhanced apoptosis rate. Conclusion: These results demonstrated that the knock-down of lncRNA ANRIL could be a potential therapeutic strategy to trigger apoptosis and circumvent doxorubicin-resistance.
Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. The objective was to investigate the role of serine/threonine kinase Pim-2 in apoptosis signal transduction pathway, because there is little study about its contribution to apoptosis in hepatocellular carcinoma.Methods: The Pim-2 gene and protein expression were examined by qRT-PCR, Western blot and immunohistochemical stain in HCC tissues and normal liver tissues. The plasmid pCI-neo-Pim2 was transfected into human hepatoma cell line SMMC7721 by lipofectamine. Total RNAs were extracted from SMMC7721 cell in logarithm growth phase. The mRNA expression of Pim-2, Akt-1 (protein kinase B), 4E-BP1 (translation repressor of mammalian target of rapamycln), SOCS-1 (repressor of cytokine), Bad(Bcl-xL/Bcl-2 associated death promoter, Bim(Bc1-2 interacting mediator of cell death)and Puma (p53 upregulated modulator of apoptosis) were identified by qRT-PCR. The cell cycle of post-transfected SMMC7721 cells was assessed by flow cytometry.Results: Pim-2 expression was enhanced in HCC. In post-transfected SMMC7721 cells, Pim-2 mRNA expression was up-regulated, level of Bad mRNA was attenuated, furthermore, the transcription level of Akt-1, SOCS-1, 4E-BP1, Bim and Puma gene wasn’t variety. Up-graulated Pim-2 can’t cause distinct change of cell cycle or apoptosis in hepatoma cell.Conclusions: The serine/threonine kinase Pim-2 plays an import role in the development of HCC, Pim-2 dependent maintenance of cell size and survival correlated with its ability to maintain down-regulated expression of the BH3 protein Bad. Pim-2 is not a trigger in cell-autonomous survival or inhibiting apoptosis in hepatocellular carcinoma. Pim-2 is a redundancy pathway of survival signaling.
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