Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma

Meng, Fei; Zhang, Luojin; Zhang, Mingjun; Ye, Kaiqin; Guo, Wei; Liu, Yu; Yang, Wulin; Zhai, Zhimin; Wang, Hongzhi; Xiao, Jun; Dai, Haiming

doi:10.1186/s12935-021-02039-y

Cited by 3 publications

(1 citation statement)

References 63 publications

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“…The BCL-RAMBO transcript is down-regulated in locally advanced rectal cancer that does not respond to chemotherapy (Millino et al, 2017). The downregulation of BCL-RAMBO is associated with a poor prognosis in clear cell and papillary renal cell carcinoma (Meng et al, 2021b). Collectively, these findings indicate that BCL-RAMBO promotes or prevents the progression of different types of cancers.…”

Section: Expression Of Bcl-rambo In Normal Cells and Cancer Cellsmentioning

confidence: 96%

Biological properties of the BCL-2 family protein BCL-RAMBO, which regulates apoptosis, mitochondrial fragmentation, and mitophagy

Kataoka

2022

Front. Cell Dev. Biol.

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Mitochondria play an essential role in the regulation of cellular stress responses, including cell death. Damaged mitochondria are removed by fission and fusion cycles and mitophagy, which counteract cell death. BCL-2 family proteins possess one to four BCL-2 homology domains and regulate apoptosis signaling at mitochondria. BCL-RAMBO, also known as BCL2-like 13 (BCL2L13), was initially identified as one of the BCL-2 family proteins inducing apoptosis. Mitophagy receptors recruit the ATG8 family proteins MAP1LC3/GABARAP via the MAP1LC3-interacting region (LIR) motif to initiate mitophagy. In addition to apoptosis, BCL-RAMBO has recently been identified as a mitophagy receptor that possesses the LIR motif and regulates mitochondrial fragmentation and mitophagy. In the 20 years since its discovery, many important findings on BCL-RAMBO have been increasingly reported. The biological properties of BCL-RAMBO are reviewed herein.

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Section: Expression Of Bcl-rambo In Normal Cells and Cancer Cellsmentioning

confidence: 96%

Biological properties of the BCL-2 family protein BCL-RAMBO, which regulates apoptosis, mitochondrial fragmentation, and mitophagy

Kataoka

2022

Front. Cell Dev. Biol.

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Significant role of circRNA BBS9 in chronic obstructive pulmonary disease via miRNA-103a-3p/BCL2L13

Guo

2023

BMC Pulm Med

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Background Various studies have shown that circular RNA (circRNA) plays a pivotal role in chronic obstructive pulmonary disease (COPD). We aimed to determine the role of circRNA BBS9 in COPD progression. Methods Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to determine the levels and the linkages of circRNA BBS9, miRNA-103a-3p, and BCL2L13 in cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cells (HPMECs). The target binding sites of circRNA BBS9 and miRNA-103a-3p were predicted using the starBase database, and the TargetScan algorithm was used to forecast the potential binding sites of BCL2L13 and miRNA-103a-3p, which were verified using a dual-luciferase reporter assay. An flow cytometry (FCM) assay was performed to determine the rate of apoptosis of HPMECs. Caspase3 activity was determined using a Caspase3 assay kit. The apoptosis-related protein bands were determined by western blotting. Results The level of circRNA BBS9 increased in 1% CSE-induced cells, and silencing of circRNA BBS9 decreased the ratio of apoptotic cells among the 1% CSE-induced HPMECs. The results of dual-luciferase reporter assays showed that miRNA-103a-3p associates with circRNA BBS9. miRNA-103a-3p was downregulated in COPD, and upregulation of miRNA-103a-3p inhibited apoptosis in CSE-stimulated cells. Moreover, BCL2L13 was found to act downstream of miRNA-103a-3p. Silencing of miRNA-103a-3p reversed the inhibitory effect of circRNA BBS9-siRNA. The effects of the miRNA-103a-3p mimic were reversed by the BCL2L13-plasmid. Conclusion circRNA BBS9 is involved in COPD development as it inhibits the functioning of miRNA-103a-3p. Our results suggest that circRNA BBS9 may act as a novel target for treating COPD.

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Functional Precision Medicine Enhances Clinical Outcomes of Relapsed/Refractory Pediatric and Adolescent Cancer Patients

Azzam,

Rocha,

Berlow

et al. 2023

Preprint

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Current genomics-driven precision oncology identifies actionable mutations in < 10% of cancer patients. Pediatric cancer is especially challenging due to limited mutations and fewer genomics-guided options. Functional precision medicine (FPM) addresses this by integrating genomic profiling with rapid, high-throughput functional ex vivo drug testing on live patient-derived cells. However, there is lack of FPM prospective data showing clinical utility in pediatric cancers. In this prospective, non-randomized, single-arm study (NCT03860376), we investigated feasibility and impact of FPM in pediatric/adolescent with refractory/relapsed solid and hematologic cancers. Of 25 patients, 19 (76%) had FPM data reviewed by the FPM tumor board within four weeks (FPMTB), meeting the primary outcome of the study. Additionally, six patients received FPM-guided treatment. Among these 6 patients, 83% (5 patients) experienced a greater than 1.3-fold improved progression-free survival compared to their previous therapy, and together demonstrated a significant increase in progression-free survival and objective response rate versus physician’s choice-treated patients (8 patients). Post-hoc analysis showed that patients with the same subtype of cancer do not cluster together, reinforcing the concept of optimizing cancer treatments one patient at a time (n-of-1 approach). Additionally, our study used a novel artificial intelligence/machine learning (AI/ML) platform that leveraged drug responses and sequencing data to identify novel biomarkers of drug efficacy and gain potential mechanistic insights within specific subsets of pediatric cancer patients. The findings from our proof-of-principle study illustrate the impact of FPM for relapsed/refractory pediatric/adolescent cancer patients, highlight future integrations of FPM and AI/ML, and support ongoing patient cohort expansion (NCT05857969).

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Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma

Cited by 3 publications

References 63 publications

Biological properties of the BCL-2 family protein BCL-RAMBO, which regulates apoptosis, mitochondrial fragmentation, and mitophagy

Biological properties of the BCL-2 family protein BCL-RAMBO, which regulates apoptosis, mitochondrial fragmentation, and mitophagy

Significant role of circRNA BBS9 in chronic obstructive pulmonary disease via miRNA-103a-3p/BCL2L13

Functional Precision Medicine Enhances Clinical Outcomes of Relapsed/Refractory Pediatric and Adolescent Cancer Patients

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