miRNA-mediated apoptosis activation through TMEM 48 inhibition in A549 cell line

Akkafa, Feridun; Koyuncu, İsmail; Temiz, Ebru; Dağlı, Hasan; Dilmeç, Fuat; Akbas, Halit

doi:10.1016/j.bbrc.2018.06.023

Cited by 17 publications

(19 citation statements)

References 20 publications

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“…Disrupted MMP increases intracellular ROS level [ 40 ], causes DNA damage [ 41 ], and subsequently activates caspases. The activated intrinsic apoptosis is critical in the initiation of ROS-mediated cell death [ 41 , 42 , 43 ]. Disruption of the mitochondrial membrane integrity leads to the activation of a number of proteins in the intermembrane space of mitochondria, resulting in alterations of BAX and BCL-2 genes expressions and release of cytochrome c [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells

Temiz

Koyuncu

Durgun

et al. 2021

IJMS

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Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells

Temiz

Koyuncu

Durgun

et al. 2021

IJMS

Self Cite

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“…All these evidences showed a role of TMEM48 in lung cancer progression (Qiao et al, 2016). A recent study demonstrated that TMEM48 suppression by miR-421 increased the expression of the apoptotic and tumor suppressor proteins caspase 3, PTEN and p53 in A549 cells (Akkafa et al, 2018). These results suggest that TMEM48 modulates the apoptotic pathway.…”

Section: Part 2: Tmems As Oncogenesmentioning

confidence: 99%

TMEM Proteins in Cancer: A Review

2018

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A transmembrane protein (TMEM) is a type of protein that spans biological membranes. Many of them extend through the lipid bilayer of the plasma membrane but others are located to the membrane of organelles. The TMEM family gathers proteins of mostly unknown functions. Many studies showed that TMEM expression can be down- or up-regulated in tumor tissues compared to adjacent healthy tissues. Indeed, some TMEMs such as TMEM48 or TMEM97 are defined as potential prognostic biomarkers for lung cancer. Furthermore, experimental evidence suggests that TMEM proteins can be described as tumor suppressors or oncogenes. TMEMs, such as TMEM45A and TMEM205, have also been implicated in tumor progression and invasion but also in chemoresistance. Thus, a better characterization of these proteins could help to better understand their implication in cancer and to allow the development of improved therapy strategies in the future. This review gives an overview of the implication of TMEM proteins in cancer.

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“…Previous studies have reported associations between many members of the TMEM family and tumor progression (Qiao et al, 2016;Gao et al, 2017;Wang et al, 2017;Akkafa et al, 2018;Song et al, 2018), but the role of TMEM205 was not previously established. In the current study, we not only found significant difference in TMEM205 expression between normal tissue and tumor tissue (p < 0.001) but also demonstrated that low TMEM205 expression was independently associated with poor OS (p = 0.032) and DSS (p = 0.002) in HCC patients from the TCGA cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, TMEM48 overexpression in lung cancer was associated with lung cancer cell proliferation, migration, and invasion (Qiao et al, 2016). Furthermore, TMEM48 suppression led to increased expression of apoptotic and tumor suppressor proteins such as caspase 3, PTEN, and p53 (Akkafa et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

TMEM205 Is an Independent Prognostic Factor and Is Associated With Immune Cell Infiltrates in Hepatocellular Carcinoma

Rao

Zhou

et al. 2020

Front. Genet.

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miRNA-mediated apoptosis activation through TMEM 48 inhibition in A549 cell line

Cited by 17 publications

References 20 publications

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells

TMEM Proteins in Cancer: A Review

TMEM205 Is an Independent Prognostic Factor and Is Associated With Immune Cell Infiltrates in Hepatocellular Carcinoma

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