bims-raghud 2026-10-11 papers

Issue of 2026–10–11
five papers selected by
Irene Sambri, TIGEM

Med Oncol. 2026 Oct 03. pii: 304. [Epub ahead of print]43(11):

TFEB promotes the progression of t(6; 11) translocation renal cell carcinoma by upregulating LINC00612 expression.

Hai-Yan Ni, Xiao-Xun Zhang, Xin-Ran Wang, Jing Ma, Xiao-Jing Yu, He-Qin Zhan.

T(6;11) translocation renal cell carcinoma (RCC) is a distinct renal tumor distinguished by the generation of Alpha-TFEB fusion gene. TFEB is highly expressed in this subtype and may drive its progression. However, its underlying mechanism remains incompletely elucidated. The current study is intended to explore whether TFEB promotes the progression of t(6;11) translocation RCC by regulating long intergenic non-protein coding RNA (LINC)00612 expression. HK-2-TFEB and Caki-2-TFEB were stably transfected cell lines with Alpha-TFEB fusion gene, which were successfully established in our research group's previous work. Western blotting was carried out to assess TFEB protein expression, and qRT-PCR was employed to measure LINC00612, microRNA (miR)-31-5p and CTNNB1 expression levels. Bioinformatics analysis, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays were employed to validate the interactions between TFEB and LINC00612, LINC00612 and miR-31-5p, as well as miR-31-5p and CTNNB1. Wound healing, CCK-8 and invasion assays were used to verify the effects exerted by LINC00612 downregulation and upregulation, as well as CTNNB1 downregulation on the biological functionalities of cells. Experiments carried out in vivo were designed to assess the effects of TFEB, LINC00612 and miR-31-5p on tumor growth. Western blotting showed high expression of TFEB in HK-2-TFEB and Caki-2-TFEB cells compared to their respective control cells. qRT-PCR revealed enhanced expression of LINC00612, decreased miR-31-5p expression and increased expression of CTNNB1 in HK-2-TFEB and Caki-2-TFEB cells. Dual-luciferase reporter and ChIP experiments confirmed that TFEB specifically bound to the promoter of LINC00612. LINC00612 overexpression in HK-2 cells enhanced cell proliferative capacity, migratory activity, and invasive potential, while its knockdown in HK-2-TFEB cells suppressed these cellular processes. LINC00612 was shown to have targeted binding to miR-31-5p, and miR-31-5p was verified to target CTNNB1. In vivo experiments demonstrated that either TFEB or LINC00612 overexpression promoted tumor growth, whereas overexpression of miR-31-5p inhibited tumor growth. Our findings suggested that overexpression of TFEB upregulated LINC00612 expression and LINC00612 competitively inhibited miR-31-5p, which directly targeted the downstream gene CTNNB1, ultimately promoting tumor progression. TFEB/LINC00612/miR-31-5p axis may be a new molecular therapeutic target for t(6;11) translocation RCC patients.

Keywords: CTNNB1; LINC00612; T(6;11) translocation RCC; TFEB; Tumor progression; miR-31-5p

DOI: https://doi.org/10.1007/s12032-026-03411-6

Pathol Int. 2026 Oct;76(10): e70187

MITF-Overexpressing Perivascular Epithelioid Cell Tumor of the Urinary Bladder Lacking TSC1/TSC2 Alterations and TFE3 Rearrangement: A Case Report and Review of the Literature.

Ji-In Jeong, Jiwoo Lee, Mee-Hye Oh, Hyun Deuk Cho, Ji-Hye Lee, Youn Soo Jeon, Si-Hyong Jang.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms characterized by melanocytic and smooth muscle differentiation, commonly associated with TSC1/TSC2 alterations or TFE3 rearrangements. Herein, we report a rare case of urinary bladder PEComa with MITF overexpression and without identifiable TSC1/TSC2 mutations or TFE3 rearrangement. A 50-year-old man underwent partial cystectomy for a bladder mass. Histologically, the tumor was well circumscribed and composed of mixed spindle and epithelioid cells with cytologic atypia and low mitotic activity. Immunohistochemistry revealed diffuse expression of SMA, HMB45, and MITF, with negative staining for TFE3. Quantitative reverse-transcription PCR revealed increased MITF mRNA expression in PEComa tissue. Next-generation sequencing identified a truncating ATRX mutation but no alterations in TSC1/TSC2 or TFE3, and no MITF copy number gain. By Folpe criteria, the tumor was classified as malignant, whereas alternative models suggested a lower-risk category, highlighting the limitations of histologic risk stratification systems. The absence of canonical TSC/mTOR or TFE3 alterations, together with MITF overexpression, suggests a distinct molecular mechanism potentially involving dysregulation of the MiT/TFE pathway. This case expands the molecular spectrum of PEComa and supports the existence of a MITF-driven subset, highlighting the need for integrated histologic and molecular evaluation for prognostic assessment.

DOI: https://doi.org/10.1111/pin.70187

J Cardiovasc Transl Res. 2026 Oct 08. pii: 132. [Epub ahead of print]19(1):

YAP and WWTR1/TAZ Connect Mechanotransduction and Mitochondrial Metabolism in Cardiac Hypertrophy and Ventricular Remodeling.

Feihu Yu, Zuqiu Liu, Jimiao Qiu, Huashan Chen, Xiaowei Song, Songqun Huang, Changjin Li.

Cardiac hypertrophy is a mechanometabolic remodeling process shaped by mechanical load, matrix stiffness and mitochondrial adaptation. YAP and TAZ, encoded by YAP1 and WWTR1, are paralogous, non-DNA-binding transcriptional co-activators that link cytoskeletal tension to TEAD-dependent transcription. This review organizes current evidence along a mechanical stress-YAP/TAZ activation-mitochondrial remodeling-ventricular remodeling axis and distinguishes direct human myocardial data, animal cardiac mechanisms, related cardiovascular or in vitro evidence, and cross-disease extrapolation. Experimental studies suggest that TEAD1 supports mitochondrial gene programs, transient YAP activation promotes glycolytic compensation during early pressure overload, whereas sustained Yap1 activation may impair mitochondrial biogenesis. Cell-specific studies further implicate fibroblast, endothelial, immune and epicardial programs, although many data derive from non-hypertrophic contexts. Thus, the adaptive-to-maladaptive YAP/TAZ model remains provisional. Human lineage-resolved data are limited, and no YAP/TAZ-targeted therapy is established for cardiac hypertrophy.

Keywords: Cardiac fibrosis; Cardiac hypertrophy; Heart failure; Mechanotransduction; Mitochondrial metabolism; Mitochondrial quality control; WWTR1; YAP/TAZ

DOI: https://doi.org/10.1007/s12265-026-10858-5

iScience. 2026 Oct 16. 29(10): 117517

RhoA through its various effectors mediate mitochondrial fragmentation in polycystic kidney disease.

Rohankrishna Harikumar, Zsuzsanna Lichner, Chen Tuo, Kuiru Wei, Ella Grieve, Rola M Saleeb, Andrew Wilde, Katalin Szászi, András Kapus.

Polycystic kidney disease (PKD), the most common genetic nephropathy, is caused by the loss/loss of function of polycystin-1 (PC1) or 2 (PC2) and characterized by cyst formation and fibrosis. A key feature of PKD is mitochondrial fragmentation, but the underlying mechanism is unknown. Since PC1/PC2 loss induces RhoA activation and fibrogenesis, we hypothesized that RhoA might also trigger general and/or PC1/2 loss-induced mitochondrial fragmentation. We show that RhoA activation is sufficient to induce DRP1-mediated mitochondrial fission in tubular cells. Importantly, genetic or pharmacologic inhibition of RhoA or its effectors (ROCK/LIM kinase/cofilin, phospho-myosin or formins) prevents/reverses PC1/PC2 loss-provoked fragmentation. Fragmentation by active formins requires F-actin polymerizing capacity but not binding to INF2, a RhoA-independent, fission-mediating formin. PC1 re-expression or RhoA/RhoA effector inhibition restores mitochondrial morphology in human PKD cells. Mitochondrial fragmentation facilitates fibrogenesis. Thus, RhoA regulates mitochondrial shape, and RhoA-mediated actin polymerization/myosin activation is a central mechanism of PKD-associated mitochondrial fragmentation.

Keywords: Drp1; Rho-signaling; RhoA small GTPase; actin; cytoskeleton; fibrosis; formins; mitochondrial fragmentation; myosin; polycystic kidney disease

DOI: https://doi.org/10.1016/j.isci.2026.117517

Mol Biol Rep. 2026 Oct 07. pii: 1675. [Epub ahead of print]53(1):

Mitochondrial dysfunction of renal tubular epithelial cells in chronic kidney disease-associated fibrosis: from organelle homeostasis to multicellular remodeling.

Shaodan Ni, Zhipeng Li, Xiaolin Pan, Yijia Zhang, Xiaoli Nie.

Chronic kidney disease (CKD) is a major global health burden, and renal fibrosis is a common pathological correlate of progressive loss of kidney function. Renal tubular epithelial cells (RTECs), particularly proximal tubular epithelial cells (PTECs), contain abundant mitochondria and depend on oxidative metabolism to support solute transport. This metabolic specialization renders them vulnerable to hypoxia, lipotoxicity, uremic toxins, aging, inflammation, and hemodynamic stress. Persistent mitochondrial injury can suppress fatty acid oxidation and oxidative phosphorylation, deplete nicotinamide adenine dinucleotide, increase mitochondrial reactive oxygen species, destabilize mitochondrial DNA, and disrupt biogenesis, dynamics, mitochondria-associated membrane signaling, and mitophagy. These abnormalities promote maladaptive repair, senescence, inflammatory cell death, and paracrine signaling to fibroblasts, macrophages, endothelial cells, and pericytes. Evidence is organized within a tubule-to-niche framework that distinguishes causal perturbation from temporal or transcriptomic association, model-specific findings from cross-model convergence, and experimental efficacy from clinical translation. Single-cell, spatial, and organoid studies are considered alongside evidence from human biopsy specimens and biomarkers. Mitochondrial dysfunction is thus treated as a context-dependent contributor to, and amplifier of, CKD-associated fibrotic remodeling rather than a universal initiating event. Although strategies targeting bioenergetics, redox balance, mitochondrial quality control, and tubular delivery are promising, translation is constrained by disease heterogeneity, intervention timing, target specificity, pharmacokinetics, and the scarcity of validated human antifibrotic endpoints.

Keywords: Chronic kidney disease; Mitochondrial dysfunction; Multicellular remodeling; Organelle homeostasis; Renal fibrosis; Renal tubular epithelial cells

DOI: https://doi.org/10.1007/s11033-026-12861-0