Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives

Hafezi, Shirin; Rahmani, Mohamed

doi:10.3390/cancers13061292

Cited by 126 publications

(88 citation statements)

References 107 publications

(152 reference statements)

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“…In addition, the dual-luciferase activity assay revealed that BIK was a downstream target gene of miR-338, and miR-338 could conversely modulate BIK expression. The major form of cell death is apoptosis, which is a programmed event regulated by the BCL-2 family of proteins which can be divided into two groups: the effectors and the BH3-only proteins, including BIK [ 44 ]. Previously, miR-1306-5p overexpression has been indicated to alleviate injury caused by cerebral ischemia/reperfusion in vitro by targeting BIK [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA TUG1 knockdown prevents neurons from death to alleviate acute spinal cord injury via the microRNA-338/BIK axis

Zhang

et al. 2021

Bioengineered

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Taurine up-regulated gene 1 (TUG1) is a cancer-associated long noncoding RNA (lncRNA) and engages in the development of spinal cord injury (SCI), a suffering neuropathological disorder. However, the regulatory role of TUG1 in acute SCI (ASCI) is still underdetermined. RT-qPCR and western blot analysis were applied to measure the expression of TUG1, microRNA-338 (miR-338), Bcl2-interacting killer (BIK), cleaved caspase 3 (c-caspase 3) and hypoxia-inducible factor-1 alpha (HIF-1α) in ASCI rats and hypoxic cells. Cell death was evaluated using flow cytometric analysis. The relationships among miR-338, TUG1 or BIK were confirmed by luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Accordingly, we monitored higher expression of TUG1 and BIK, but lower expression of miR-338 in ASCI rats and hypoxic cells. In vitro, hypoxia expedited cell death and c-caspase 3 levels. In vivo, ASCI rats were successfully developed as evidenced by diminished Basso-Beattie-Bresnahan (BBB) locomotor score and enhanced c-caspase 3 and HIF-1α expression. Nevertheless, TUG1 knockdown mitigated the cell death in ASCI rats and hypoxic cells. Mechanically, TUG1 interacted with miR-338 to regulate the BIK expression. Together, TUG1 silencing could alleviate the death in neurons and ASCI models via modulating the miR-338/BIK axis.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA TUG1 knockdown prevents neurons from death to alleviate acute spinal cord injury via the microRNA-338/BIK axis

Zhang

et al. 2021

Bioengineered

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“…Genes were selected after literature review and in silico analysis of the TCGA set. The bcl-2 (b cell lymphoma 2) protein encoded by BCL2 is a major apoptosis regulator and has mainly antiapoptotic effects in many different cancer entities [16]. BRCA1 and BRCA2 code for the correspondent breast cancer type 1/2 susceptibility proteins.…”

Section: Discussionmentioning

confidence: 99%

RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy

Herrmann

Schmidt

Nitschke

et al. 2021

IJMS

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Background: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. Material and methods: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). Results: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039; TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059; TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. Conclusion: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression.

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“…Total proteins were isolated from tissues and cells in RIPA reagent (Sigma-Aldrich), and 20 μg aliquot of that were subjected to western blotting assay to evaluate expression of special proteins related to apoptosis (Bcl2-associated X protein [Bax] [ 22 ]), autophagy (LC3 [ 23 ]) and metastasis (matrix metalloproteinase 9 [MMP-9] [ 24 ]). The primary antibodies including anti-LC3 (4600-1-AP, 1:2,500; Proteintech, Wuhan, China), anti-NPTX2 (10,889-1-AP, 1:1,000; Proteintech), anti-MMP9 (ab228402; 1:5,000; Abcam, Shanghai, China), anti-Bax (ab216494; 1:500; Abcam), and anti-β-actin (20,536-1-AP, 1:5,000; Proteintech) were incubated overnight at 4°C, and secondary antibody anti-Rabbit IgG (SA00001-2, 1:10,000, Proteintech) was incubated for 2 h at 25°C.…”

Section: Methodsmentioning

confidence: 99%

Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2)

Long

Jia

et al. 2021

Bioengineered

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Hsa_circ_0054537 (circ_0054537) is a novel tumor-related circular RNA in renal cell carcinoma (RCC), and we intended to ascertain its dysregulation and functions in RCC malignant progression, as well as the underlying mechanism via serving as competing endogenous RNA (ceRNA). In this research, using real-time quantitative PCR, we found circ_0054537 was upregulated in RCC tissues and cells, and distributed throughout the cytoplasm. Then, functional effects of circ_0054537 in RCC were detected using cell counting kit-8, transwell, flow cytometry and glycolysis stress test and adenosine Triphosphate (ATP) assays. The results uncovered that circ_0054537 knockdown inhibited cell proliferation, migration, invasion, autophagy and glycolysis, but promoted apoptosis in RCC cells. Notably, circ_0054537 was identified as a ceRNA for microRNA (miR)-640, and miR-640 could target neuronal pentraxin-2 (NPTX2), as evidenced by dual-luciferase reporter assay and RNA immunoprecipitation assay. Besides, miR-640 downregulation or NPTX2 overexpression partly overturned the tumor suppressor function of circ_0054537 silence and miR-640 overexpression in RCC cells. Additionally, RCC cell growth in vivo was retarded by circ_0054537 silence. In conclusion, circ_0054537/miR-640/NPTX2 ceRNA pathway regulated RCC malignant progression in vitro and curbed RCC tumor growth in vivo, which could be a potential diagnosis and therapeutic target of RCC.

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Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives

Cited by 126 publications

References 107 publications

Long non-coding RNA TUG1 knockdown prevents neurons from death to alleviate acute spinal cord injury via the microRNA-338/BIK axis

Long non-coding RNA TUG1 knockdown prevents neurons from death to alleviate acute spinal cord injury via the microRNA-338/BIK axis

RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy

Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2)

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