Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 2017.11

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  Now

  The Molecular Biology Society of Japan

• 2017.05

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  Now

  RNA Japan

• 2017.02

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  Now

  The Japanese Society for Epigenetics

• 2016.04

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  Now

  Japanese Cancer Association

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Tumor biology   non-coding RNA

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• 札幌医科大学   医学部分子生物学講座   助教  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma.

  Takeshi Niinuma, Hiroshi Kitajima, Tatsuya Sato, Toshifumi Ogawa, Kazuya Ishiguro, Masahiro Kai, Eiichiro Yamamoto, Yui Hatanaka, Iyori Nojima, Mutsumi Toyota, Akira Yorozu, Shohei Sekiguchi, Noritsugu Tohse, Masato Furuhashi, Hiroshi Ohguro, Akihiro Miyazaki, Hiromu Suzuki

  Cancer science    2024.11  [International journal]

  　View Summary

  Long noncoding RNAs (lncRNAs) play pivotal roles in the development of human malignancies, though their involvement in oral squamous cell carcinoma (OSCC) remains incompletely understood. Using The Cancer Genome Atlas (TCGA) dataset, we analyzed expression of 7840 lncRNAs in primary head and neck squamous cell carcinoma (HNSCC) and found that upregulation of LINC02154 is associated with a poorer prognosis. LINC02154 knockdown in OSCC cell lines induced cell cycle arrest and apoptosis, and significantly attenuated tumor growth in vitro and in vivo. Notably, depletion of LINC02154 downregulated FOXM1, a master regulator of cell cycle-related genes. RNA pulldown and mass spectrometry analyses identified a series of proteins that could potentially interact with LINC02154, including HNRNPK and LRPPRC. HNRNPK stabilizes FOXM1 expression by interacting with the 3'-UTR of FOXM1 mRNA, which suggests LINC02154 and HNRNPK promote cell cycling by regulating FOXM1 expression. Additionally, LINC02154 positively regulates HNRNPK expression by inhibiting microRNAs targeting HNRPNK. Moreover, LINC02154 affects mitochondrial function by interacting with LRPPRC. Depletion of LINC02154 suppressed expression of mitochondrial genes, including MTCO1 and MTCO2, and inhibited mitochondrial respiratory function in OSCC cells. These results suggest that LINC02154 exerts its oncogenic effects by modulating the cell cycle and oxidative phosphorylation in OSCC, highlighting LINC02154 as a potential therapeutic target.

  DOI PubMed

• AEBP1 is a negative regulator of skeletal muscle cell differentiation in oral squamous cell carcinoma.

  Fumika Okazaki, Akira Yorozu, Shohei Sekiguchi, Takeshi Niinuma, Reo Maruyama, Hiroshi Kitajima, Eiichiro Yamamoto, Kazuya Ishiguro, Mutsumi Toyota, Yui Hatanaka, Koyo Nishiyama, Kazuhiro Ogi, Masahiro Kai, Kenichi Takano, Shingo Ichimiya, Akihiro Miyazaki, Hiromu Suzuki

  Scientific reports   14 ( 1 ) 27425 - 27425  2024.11  [International journal]

  　View Summary

  The tumor microenvironment plays a pivotal role in cancer development. We recently reported that in oral squamous cell carcinoma (OSCC), adipocyte enhancer-binding protein 1 (AEBP1) is abundantly expressed in cancer-associated fibroblasts (CAFs), leading to CAF activation and inhibition of CD8 + T cell infiltration. In the present study, we investigated whether AEBP1 contributes to the destruction and atrophy of muscle tissues in OSCC. By analyzing human skeletal muscle myoblasts (HSMMs), we found that AEBP1 is downregulated during muscle cell differentiation. Transcriptome analysis revealed that AEBP1 knockdown significantly upregulates myogenesis-related genes in HSMMs, and qRT-PCR and western blot analyses confirmed the induction of muscle-related genes, including MYOG, in HSMMs after AEBP1 knockdown. Conversely, ectopic expression of AEBP1 strongly suppressed myogenesis-related genes in HSMMs. Notably, indirect co-culture of HSMMs with OSCC cells led to AEBP1 upregulation and robust suppression of muscle-related genes in HSMMs. Treatment with TGF-β1 also upregulated AEBP1 and suppressed expression of muscle-related genes in HSMMs. Our findings suggest that AEBP1 is a negative regulator of skeletal muscle cell differentiation and that OSCC cells inhibit muscle cell differentiation, at least in part, by inducing AEBP1.

  DOI PubMed

• Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas.

  Hironori Aoki, Akira Takasawa, Eiichiro Yamamoto, Takeshi Niinuma, Hiro-O Yamano, Taku Harada, Toshiyuki Kubo, Akira Yorozu, Hiroshi Kitajima, Kazuya Ishiguro, Masahiro Kai, Akio Katanuma, Toshiya Shinohara, Hiroshi Nakase, Tamotsu Sugai, Makoto Osanai, Hiromu Suzuki

  BMC gastroenterology   24 ( 1 ) 91 - 91  2024.03  [International journal]

  　View Summary

  BACKGROUND: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. METHODS: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). RESULTS: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. CONCLUSION: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

  DOI PubMed

• TM4SF1-AS1 inhibits apoptosis by promoting stress granule formation in cancer cells

  Hiroshi Kitajima, Reo Maruyama, Takeshi Niinuma, Eiichiro Yamamoto, Akira Takasawa, Kumi Takasawa, Kazuya Ishiguro, Akihiro Tsuyada, Ryo Suzuki, Gota Sudo, Toshiyuki Kubo, Kei Mitsuhashi, Masashi Idogawa, Shoichiro Tange, Mutsumi Toyota, Ayano Yoshido, Kohei Kumegawa, Masahiro Kai, Kazuyoshi Yanagihara, Takashi Tokino, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

  Cell Death & Disease ( Springer Science and Business Media LLC )  14 ( 7 )  2023.07

  　View Summary

  Abstract Long noncoding RNAs (lncRNAs) play pivotal roles in tumor development. To identify dysregulated lncRNAs in gastric cancer (GC), we analyzed genome-wide trimethylation of histone H3 lysine 4 (H3K4me3) to screen for transcriptionally active lncRNA genes in the non-tumorous gastric mucosa of patients with GC and healthy individuals. We found that H3K4me3 at TM4SF1-AS1 was specifically upregulated in GC patients and that the expression of TM4SF1-AS1 was significantly elevated in primary and cultured GC cells. TM4SF1-AS1 contributes to GC cell growth in vitro and in vivo, and its oncogenic function is mediated, at least in part, through interactions with purine-rich element-binding protein α (Pur-α) and Y-box binding protein 1 (YB-1). TM4SF1-AS1 also activates interferon signaling in GC cells, which is dependent on Pur-α and RIG-I. Chromatin isolation by RNA purification (ChIRP)-mass spectrometry demonstrated that TM4SF1-AS1 was associated with several stress granule (SG)-related proteins, including G3BP2, RACK1, and DDX3. Notably, TM4SF1-AS1 promoted SG formation and inhibited apoptosis in GC cells by sequestering RACK1, an activator of the stress-responsive MAPK pathway, within SGs. TM4SF1-AS1-induced SG formation and apoptosis inhibition are dependent on Pur-α and YB-1. These findings suggested that TM4SF1-AS1 contributes to tumorigenesis by enhancing SG-mediated stress adaptation.

  DOI

• Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers.

  Ayano Yoshido, Gota Sudo, Akira Takasawa, Hironori Aoki, Hiroshi Kitajima, Eiichiro Yamamoto, Takeshi Niinuma, Taku Harada, Toshiyuki Kubo, Hajime Sasaki, Kazuya Ishiguro, Akira Yorozu, Masahiro Kai, Akio Katanuma, Hiro-O Yamano, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

  Journal of gastroenterology and hepatology   38 ( 2 ) 301 - 310  2022.11  [International journal]

  　View Summary

  BACKGROUND AND AIM: The tumor microenvironment plays an essential role in the development and progression of colorectal cancer (CRC). We recently reported that crosstalk between CRC cells and tumor-associated macrophages (TAMs) via serum amyloid A1 (SAA1) promotes invasion by T1 CRCs. In the present study, we aimed to clarify the role of neutrophils in early CRCs. METHODS: Immunohistochemical analysis of CD66b, chemokine CXC motif ligand 8 (CXCL8 or interleukin-8, IL-8) and matrix metalloproteinase-9 (MMP-9) was performed using primary T1 CRCs (n = 49). The HL-60 human promyelocytic leukemia cell line and THP-1 human monocytic leukemia cell line were used to obtain neutrophil-like and macrophage-like cells, respectively. Boyden chamber assays were used to analyze cell migration and invasion, and quantitative RT-PCR was used to analyze gene expression. RESULTS: Immunohistochemical analysis revealed accumulation of neutrophils at the SAA1-positive invasive front of T1 CRCs. Experiments using HL-60 cells suggested that treatment with SAA1 induced neutrophil migration and expression of CXCL8 and MMP-9 in neutrophils and that neutrophils promote CRC cell migration and invasion. Immunohistochemistry confirmed accumulation of CXCL8- or MMP-9-positive neutrophils at the SAA1-positive invasive front of T1 CRCs. Moreover, co-culture experiments using CRC, THP-1 and HL-60 cells suggested that CRC cells activated by macrophages upregulate CXCL8 and MMP-9 in neutrophils. CONCLUSIONS: Our results suggest that interplay between macrophages and CRC cells leads to recruitment of neutrophils to the invasive front of T1 CRCs and that SAA1 secreted by CRC cells activate neutrophils to promote invasion.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Development of a new combinational epigenetic therapy of multiple myeloma

  石黒一也, 石黒一也, 北嶋洋志, 新沼猛, 石田禎夫, 丸山玲緒, 池田博, 山本英一郎, 山本英一郎, 甲斐正広, 佐々木泰史, 時野隆至, 仲瀬裕志, 鈴木拓

  日本癌学会学術総会抄録集(Web)   78th  2019

  J-GLOBAL

• 臨床医学の最新情報 がんのnon-coding RNA異常およびエピゲノム異常の解析とその応用

  鈴木 拓, 新沼 猛, 北嶋 洋志, 山本 英一郎, 甲斐 正広, 高橋 秀明, 伊東 文生

  電気泳動 ( 日本電気泳動学会 )  62 ( Suppl. ) s23 - s23  2018.08

• 胃がん発生に関与する長鎖non-coding RNAの同定

  北嶋 洋志, 丸山 玲緒, 山本 英一郎, 新沼 猛, 甲斐 正広, 時野 隆至, 仲瀬 裕志, 鈴木 拓

  生命科学系学会合同年次大会 ( 生命科学系学会合同年次大会運営事務局 )  2017年度   [2P - 0828]  2017.12

• 大腸がんにおける腫瘍血管内皮関連遺伝子の同定

  萬 顕, 山本 英一郎, 沼田 有斗, 新沼 猛, 北嶋 洋志, 甲斐 正広, 青木 敬則, 若杉 英樹, 時野 隆至, 中瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事 ( 日本癌学会 )  76回   P - 2224  2017.09

• 大腸がんにおけるDiacylglycerol kinase γのエピジェネティックな不活性化

  甲斐 正広, 山本 英一郎, 佐藤 亜紀子, 山野 泰穂, 新沼 猛, 北嶋 洋志, 原田 拓, 青木 敬則, 仲瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事 ( 日本癌学会 )  76回   J - 2093  2017.09

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Industrial Property Rights 【 display / non-display 】

Industrial Property Rights 【 display / non-display 】

• 長鎖ノンコーディングRNAを標的とするがん治療剤およびがん診断方法

  特許7319688

  北嶋洋志, 丸山玲緒, 山本英一郎, 鈴木拓

  Patent

• 長鎖ノンコーディングＲＮＡを標的とするがん治療剤およびがん診断

  北嶋洋志, 丸山玲緒, 山本英一郎, 鈴木拓

  Patent

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Identification of colorectal cancer-associated microproteins translated from noncoding RNAs

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2024.04

  -

  2027.03

   

  北嶋 洋志, 高澤 啓, 新沼 猛

• DOT1L阻害によるインターフェロン応答の機序解明とがん免疫療法への応用

  基盤研究(B)

  Project Year :

  2022.04

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  2025.03

   

  鈴木 拓, 仲瀬 裕志, 新沼 猛, 北嶋 洋志

• 胃がん関連長鎖non-coding RNAによるストレス顆粒と発がん機構の解析

  基盤研究(C)

  Project Year :

  2021.04

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  2024.03

   

  北嶋 洋志, 鈴木 拓

  Authorship： Principal investigator

  　View Summary

  申請者らは先行実験により慢性胃炎および胃がんで発現が亢進する長鎖non-coding RNA (lncRNA) TM4SF1AS1がストレス顆粒の形成促進とアポトーシスの抑制に関与することを明らかにしたが、その詳細なメカニズムは不明である。本研究はその分子機構を明らかにすることを目的としている。 TM4SF1AS1の詳細な細胞内の局在情報を得るために、MS2タグを付加したTM4SF1AS1のTet-on遺伝子発現誘導系胃がん細胞株を樹立し、免疫蛍光染色を行った。ストレス顆粒マーカーであるTIA-1、G3BP1やG3BP2と共にTM4SF1AS1がその過剰発現によって形成された顆粒様構造に局在することが示された。 また、TM4SF1AS1との相互作用が見られたRACK1は、MTK1の活性化からp38/JNKを介したアポトーシスを引き起こすが、ストレス顆粒はRACK1を顆粒内に隔離しアポトーシスを抑制することが知られる。TM4SF1AS1の過剰発現により形成されたストレス顆粒にRACK1が局在したことから、がん細胞におけるTM4SF1AS1によるストレス顆粒の機能として、生存に不利に働くタンパク質や転写産物を隔離しその機能の阻害や翻訳を抑制することが考えられた。 そこでTM4SF1AS1と相互作用し翻訳抑制を受ける可能性のあるRNA分子の探索を、ChIRP RNA-seqにより試みた。結果585個の候補が得られ、その三分の一がmRNAに該当した。Gene Ontology解析を行った結果、アポトーシスに関連するmRNAがエンリッチしていた。一部のアポトーシス関連mRNAがTM4SF1AS1の標的となり翻訳抑制を受ける可能性があると考えられることから、さらなる解析を進める。

• Revealing the function and the molecular network of a novel lncRNA associated with gastric cancer and gastritis

  Grant-in-Aid for Early-Career Scientists

  Project Year :

  2018.04

  -

  2020.03

   

  Kitajima Hiroshi

  　View Summary

  Gastric cancers (GCs) develop through Helicobacter Pylori-induced chronic gastritis. The involvement of long noncoding RNAs (lncRNAs) in inflammation-related carcinogenesis remains unclear. We have identified a lncRNA TM4SF1AS1, which promotes GC cell proliferation and tumor formation. To unravel pathways and molecular networks associated with TM4SF1AS1 in the tumorigenesis, we comprehensively screened a series of TM4SF1AS1-binding proteins. We identified many stress granule-associated molecules and found that TM4SF1AS1 promoted stress granule-like bodyformation in GC cells. Moreover, TM4SF1AS1 inhibited apoptosis mediated by stress-responsive MAPK. It suggested that TM4SF1AS1 might be a lncRNA link between tumorigenesis and stress granule and a potential therapeutic target.

Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• SMOC1の大腸腫瘍診断マーカーとしての臨床的有用性の検討

  青木 敬則, 山本 英一郎, 高澤 啓, 新沼 猛, 山野 泰穂, 萬 顕, 北嶋 洋志, 甲斐 正広, 小山内 誠, 仲瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事  (一社)日本癌学会

  Presentation date： 2021.09

  Event date：

  2021.09

  　

  　

• SMOC1の大腸腫瘍診断マーカーとしての臨床的有用性の検討

  青木 敬則, 山本 英一郎, 高澤 啓, 新沼 猛, 山野 泰穂, 萬 顕, 北嶋 洋志, 甲斐 正広, 小山内 誠, 仲瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事  (一社)日本癌学会

  Presentation date： 2020.10

  Event date：

  2020.10

  　

  　

• 臨床医学の最新情報 がんのnon-coding RNA異常およびエピゲノム異常の解析とその応用

  鈴木 拓, 新沼 猛, 北嶋 洋志, 山本 英一郎, 甲斐 正広, 高橋 秀明, 伊東 文生

  電気泳動  日本電気泳動学会

  Presentation date： 2018.08

  Event date：

  2018.08

  　

  　

• 胃がん発生に関与する長鎖non-coding RNAの同定

  北嶋 洋志, 丸山 玲緒, 山本 英一郎, 新沼 猛, 甲斐 正広, 時野 隆至, 仲瀬 裕志, 鈴木 拓

  生命科学系学会合同年次大会  生命科学系学会合同年次大会運営事務局

  Presentation date： 2017.12

  Event date：

  2017.12

  　

  　

• SMOC1のエピジェネティックなサイレンシングは大腸鋸歯状腺腫の発育進展に関連する

  青木 敬則, 山本 英一郎, 高澤 啓, 新沼 猛, 山野 泰穂, 原田 拓, 萬 顕, 北嶋 洋志, 甲斐 正広, 澤田 典均, 仲瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事  日本癌学会

  Presentation date： 2017.09

  Event date：

  2017.09

  　

  　

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