大阪大学 · 生化学・遺伝学・分子生物学
景久教授の研究室は、がん微小環境の解明を目的として、手術により切除された腫瘍組織から直接抽出した腫瘍由来の細胞外小胞(Te-EV)を用いたタンパク質・マイクロRNAの解析を進めています。特に、腫瘍特異的因子(AZU1、LAIR1、miR-629、miR-122など)が腫瘍の進行や転移に果たす役割を分子機構レベルで解明しており、がんのバイオマーカーとしての応用も視野に入れています。また、血液中の細胞外小胞に由来する腸内細菌由来DNAの存在や、がんにおけるシグナル経路(TGFβ/Smad、Wnt/β-カチニン)の制御機構についても、新規の治療的標的の同定を目指した研究を展開しています。
Figures are computed from collected data and may differ slightly.
Cancer-associated extracellular vesicles (EVs) are intimately involved in establishment of tumor microenvironment and occurrence of metastasis. However, previous studies have mainly relied on experiments with cultured cell lines or mouse models, making it difficult to gain a full understanding of EV functions in human body. Hence, we extracted EVs directly from surgically resected viable clear cell renal cell carcinoma (ccRCC) tissues and adjacent normal renal tissues (n = 20). Quantitative LC/M
This study suggests that miR-629 has biomarker potential through its ability to regulate TGFβ/Smad signaling and accelerate ccRCC cell motility and invasion.
Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. Although several studies have reported high expression of miR-122 in ccRCC, its physiological role remains unclear. To clarify the role of miR-122 in ccRCC, we compared miR-122 expression levels in non-cancerous tissue and ccRCC. Significant upregulation of miR-122 was observed in ccRCC specimens. Moreover, ccRCC patients with high miR-122 expres
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 90‑95% of cases. We previously reported a novel method that enables direct extraction of extracellular vesicles (EVs) from surgically resected viable tissues, yielding what we term tissue‑exudative extracellular vesicles (Te‑EVs). Quantitative LC/MS analysis identified 3,871 proteins in Te‑EVs, among which leukocyte‑associated immunoglobulin‑like receptor 1 (LAIR1) was highly enriched in
Differentiation-inducing factor-1 (DIF-1), a morphogen for Dictyostelium discoideum, inhibits the proliferation of human cancer cell lines by suppressing the Wnt/β-catenin signaling pathway. In this study, we examined the effect of DIF-1 on c-Myc, a target gene product of the Wnt/β-catenin signaling pathway, mainly using HCT-116 colon cancer cells. DIF-1 strongly reduced the amount of c-Myc protein in time- and concentration-dependent manners and reduced c-Myc mRNA expression by inhibiting promo
Bacterial flora are present in various parts of the human body, including the intestine, and are thought to be involved in the etiology of various diseases such as multiple sclerosis, intestinal diseases, cancer, and uterine diseases. In recent years, the presence of bacterial 16S rRNA genes has been revealed in blood, which was previously thought to be a sterile environment, and characteristic blood microbiomes have been detected in various diseases. However, the mechanism and the origin of the
Abstract The human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via ce
Previously, we have revealed that the miR-130 family (miR-130b, miR-301a, and miR-301b) functions as an oncomiR in bladder cancer. The pharmacological inhibition of the miR-130 family molecules by the seed-targeting strategy with an 8-mer tiny locked nucleic acid (LNA) inhibits the growth, migration, and invasion of bladder cancer cells by repressing stress fiber formation. Here, we searched for a functionally advanced target sequence with LNA for the miR-130 family with low cytotoxicity and fou
Analysis of ovarian cancer tissue and normal ovarian tissue revealed 31 RNA modifications with significant differences observed in cancer tissue compared with normal tissue. Moreover, we found Im and chm5U as characteristic RNA modifications in advanced and platinum-resistant ovarian cancers, respectively. Considering that these differences in RNA modifications may be due to the intra-tumour microenvironment, we xenografted the ovarian cancer cell line RMG-1 to create RMG-1 tumours and compared
Azurocidin (AZU1) is an antimicrobial protein secreted by neutrophils that acts as a chemoattractant for monocytes and macrophages and a permeabilizer of vascular endothelial cells. We previously identified AZU1 to be specifically present in extracellular vesicles (EVs) obtained from renal cell carcinoma (RCC) tissues. Here, we examined the relationship between N-linked glycosylation and AZU1 loading into small EVs (SEVs). Inhibition of N-linked glycosylation by introducing mutations in three gl
RNA modifications are crucial in cellular processes, and their dysregulation is linked to diseases like cancer. Extracellular vesicles (EVs) contain various RNAs and might be susceptible to modifications, but detecting these modifications has been challenging due to the small amount of RNA in EVs. We successfully detected 22 RNA modifications in EVs using a proprietary ultra-HPLC MS/MS system. We identified reduced levels of N6-methyladenosine (m6A) in EVs derived from colon cancer tissues, whic
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