Yamaguchi University Navigator for Open access Collection and Archives

岡田, 菜穂子

櫻井, 凜

柳下, 雅子

松尾, 理佳

田中, 美穂

田中, 亜矢巳

Undetermined

障害学生修学支援ニーズと修学スケジュールの関連性 : 山口大学の事例から

博士(医学)山口大学Yamaguchi Universit

中村, 克彦

A Novel Index Including Age, Sex, hTERT, and Methylated RUNX3 Is Useful for Diagnosing 
Early Gastric Cancer 



English

年齢，性別，hTERT，メチル化RUNX3 を含む新しい指標は早期胃癌の診断に有用である

博士(工学)山口大学Yamaguchi Universit

北田, 達也

Catalan

高浸透性型けい酸塩系改質材を用いた火害を受けたコンクリートの補修技術に関する研究

博士(獣医学)山口大学Yamaguchi Universit

樋野, 裕則

( 3 ) 
( 2,000 800 ) 
Role of Hypoxia-Regulated Non-Coding RNA Molecules in Canine Oral Melanoma 
RNA
Canine oral melanoma (COM) is an aggressive malignancy characterized by rapid 
progression and a high propensity for metastasis. The hypoxic tumor microenvironment 
is critical to COM's invasive behavior, influencing gene expression and cellular signaling 
pathways. Non-coding RNA molecules, including microRNAs (miRNAs) and long non-
coding RNAs (lncRNAs), are known to play pivotal roles in tumor adaptation to hypoxia. 
However, their specific regulatory mechanisms in COM remain poorly understood. This 
dissertation investigates the roles of hypoxia-regulated non-coding RNA molecules, 
elucidating their contributions to COM progression and their potential as diagnostic 
biomarkers and therapeutic targets.   
In the first chapter, I studied the dysregulated hypoxia-related micro RNA in cCOM. 
Hypoxia contributes significantly to the progression and metastasis of COM by inducing 
miRNA expression changes that regulate critical oncogenic pathways. This chapter 
explores the expression profiles of hypoxia-regulated microRNAs (HRMs) in canine oral 
melanoma using primary-site (KMeC) and metastatic (LMeC) COM cell lines cultured 
under normoxic (21% O2) and hypoxic (2% O2) conditions. Next-generation sequencing 
(NGS) and subsequent qPCR validation identified a set of hypoxia-regulated miRNAs, 
including miR-21, miR-210, and miR-301a, all exhibiting significant upregulation under 
hypoxic conditions. 
Notably, miR-210, a well-known hypoxia marker, showed progressive upregulation, 
confirming its role in hypoxia-induced signaling. miR-21, identified as a central hub in 
the miRNA regulatory network, targeted vital oncogenes such as VEGF, PTEN, and 
TGFBR2, promoting angiogenesis, metastasis, and cell survival. miR-301a, uniquely 
active in metastatic cell lines, was implicated in aggressive cancer phenotypes by 
regulating pathways like MAPK1 and cyclin-dependent kinases. Network analyses using 
KEGG pathways and miRNet highlighted the complex interplay between these HRMs and 
critical oncogenic signaling cascades.
In this chapter, I concluded that hypoxia-induced miRNA dysregulation drives tumor 
progression by influencing cell survival, angiogenesis, and metastasis pathways. These 
HRMs serve as potential biomarkers for hypoxic adaptation and targets for therapeutic 
( 3 ) 
( 2,000 800 ) 
intervention. 
In my second chapter, building on the findings from Chapter 1, I studied the 
dysregulated hypoxia-related lncRNAs in cCOM. Using transcriptomic profiling via 
NGS, numerous lncRNAs were found to be dysregulated under hypoxic conditions in 
both primary and metastatic COM cell lines and in clinical tumor tissues. Among 
these, a novel lncRNA fragment, ENSCAFT00000084705.1, emerged as a significant 
molecule of interest. 
ENSCAFT00000084705.1 was consistently downregulated under hypoxic 
conditions in both primary-site (KMeC) and metastatic (LMeC) COM cells and in 
COM clinical tissue samples compared to normal oral tissue. This downregulation 
was validated through qPCR, demonstrating progressive suppression of 
ENSCAFT00000084705.1 expression with increased hypoxic exposure. Interestingly, 
its absence in plasma and extracellular vesicles indicated that this lncRNA is tumor-
specific and unsuitable as a circulating biomarker. 
Functional exploration suggested that ENSCAFT00000084705.1 may play a role 
in regulating hypoxia-induced metastasis and tumor aggression. While its exact 
molecular function remains to be elucidated, its consistent expression pattern 
highlights its potential significance in COM biology. The findings emphasize the need 
for further research into lncRNAs as contributors to hypoxia-driven tumor adaptation 
and as targets for novel therapeutic strategies. 
In conclusion, I elucidate the critical roles of hypoxia-regulated non-coding RNA 
molecules in canine oral melanoma, emphasizing both microRNAs and long non-
coding RNAs. The identification of miR-21, miR-210, and miR-301a as critical 
players in hypoxia-induced oncogenic pathways and the discovery of the lncRNA 
ENSCAFT00000084705.1 as a hypoxia-specific regulator provide valuable insights 
into COM biology. These findings highlight the complex interplay between the tumor 
microenvironment and non-coding RNA-mediated gene regulation. Collectively, this 
research contributes to the understanding of hypoxia-driven mechanisms in COM 
progression and underscores the potential of non-coding RNAs as biomarkers and 
therapeutic targets for this aggressive cancer. 




犬のメラノーマにおける低酸素環境下で調節される非コードRNA分子の役割

SHELLY WULANDARI

(Appended form No. 3) 
(About 800 words in English) 
Abstract of Doctoral Thesis 
Name SHELLY WULANDARI 
Title: Establishment of a reverse genetic system and determination of the responsible gene for the 
 enhanced virulence of trisegmented bunyaviruses. 
 (3
) 
Abstract of thesis: 
 Trisegmented bunyaviruses constitute a category of viruses within the  order, 
distinguished by their segmented, negative-sense RNA genomes that are encoded in an orientation opposite 
to that of messenger RNA. Their members infect broad ranges of hosts, including several significant human 
pathogens. Reverse genetic systems have been essential in the investigation of trisegmented bunyaviruses. 
The process of introducing a precise genetic change into a viral genome, known as viral reverse genetics, 
has revolutionized our understanding of negative-sense, segmented RNA viruses. While the specific 
characteristics of reverse genetic systems vary among different viruses, the fundamental principles of 
biology remain the same. Here, we examine the development of reverse genetic systems as applied to these 
virus members, emphasizing conserved approaches illustrated by some of the prominent members that 
cause significant human disease. We also describe the utility of their genetic systems in the determination 
of the responsible gene for the enhanced virulence of trisegmented bunyaviruses.   
 The genus Orthonairovirus includes highly pathogenic tick-borne viruses, such as the Crimean-
Congo hemorrhagic fever orthonairovirus (CCHFV). A reverse genetics system is an indispensable tool for 
determining the viral factors related to pathogenicity. Tofla orthonairovirus (TFLV) is a recently identified 
virus isolated from ticks in Japan, and our research has suggested that TFLV is a useful model for studying 
pathogenic orthonairoviruses. In this study, we successfully established a reverse genetics system for TFLV 
using T7 RNA polymerase. Recombinant TFLV was generated by transfecting cloned complementary 
DNAs encoding the TFLV genome into BSR T7/5 cells expressing T7 RNA polymerase. We were able to 
rescue infectious recombinant TFLV mutant (rTFLVmt) and wild-type TFLV (rTFLVpt) viruses, which 
exhibited indistinguishable growth kinetics in mammalian cells and pathogenicity in A129 mice compared 
with the authentic virus. Our approach provides a valuable method for establishing a reverse genetic system 
for orthonairoviruses. 
  Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with 
a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute 
to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. 
Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no 
fatality. We identified a pair of amino acid residues in the Gc protein, glycine and serine, at residues 581 
(Appended form No. 3) 
(About 800 words in English) 
and 934, respectively, derived from Tk-F123, leading to a fatal infection. Those in Ng-F264 were arginine 
and asparagine. These results suggest that this pair of residues affects the Gc protein function and regulates 
SFTSV virulence. Our findings provide useful clues for the elucidation of viral pathogenicity and the 
development of effective live-attenuated vaccines and antiviral strategies. 
 In conclusion, we were able to rescue recombinant TFLV and SFTSV from cDNA clones, allowing 
detailed studies on viral genetics and pathogenesis. We also describe the molecular determinants of virulence 
in SFTSV, which is crucial for developing effective vaccines and therapeutics. Finally, we highlight that 
reverse genetics continues to be a powerful tool in elucidating the molecular mechanisms of virulence in 
trisegmented bunyaviruses, which will contribute to our understanding of viral biology, pathogenesis, and 
intervention strategies.





3分節ゲノムを有するブニヤウイルスを対象としたリバースジェネティクス系の確立および病原性に関与するウイルス遺伝子の特定

博士(学術)山口大学Yamaguchi Universit

礒田, 将史

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Icelandic

国際的視点からみる地方都市港湾の機能転換－再開発・住民参加・交流事業―

藤上, 真弓

総合的な学習の時間の話し合い場面における「協働」の質を高める授業づくり支援に関する研究

高橋, 征仁

Japanese

都市における自己家畜化 : 結婚を介した「向社会性」の2重相続仮説に関する検討

横山, 成己

- 38 -
11．馬術部倉庫裏周辺排水改善対策工事に伴う立会調査
調査地区 吉田構内Ｍ－７区
調査面積 20㎡
調査期間 令和４年３月２日
調査担当 横山成己
調査結果
令和３年度後半、学生支援部と共同獣医学部の
連名で、吉田構内北端部に位置する体育会馬術部
厩舎北東側に排水溝を新設する工事計画が立案さ
れた（図29）。馬場と南西に設けられている厩舎とは
約２ｍの高低差があり、降雨時に馬場法面を通じて
厩舎周囲に雨水が溜まることが原因であった。
構内北端部にある馬術部および自動車部敷地
は、姫山から南西に派生する丘陵谷筋の一つに設
けられており、谷筋南東丘陵の北西斜面の立会調
査以外にさしたる調査歴もないことから、小規模な
註1
掘削でも地下の様相を確認する必要があると判断さ
れたため、掘削時に立会調査を実施することが第３
回埋蔵文化財資料館専門委員会（12月３日（月）～
メール審議）にて諮られ、承認された。
馬場南西法面については、除草後にバックホー
バケットおよびランマープレートにより転圧がかけら
れたことから、土層断面は観察できなかった。周辺
地形からみて馬場南西部は盛土による嵩上げが行
われている可能性が高い。排水溝底面部は現地表
下25㎝の掘削が行われたが、盛土内に止まった（図
30、写真82）。
当谷筋の北西丘陵部南東斜面には、７基からな
る日吉神社横穴墓群のうち６基が分布している。谷
筋については、本学により構内造成時に大規模な
土地改変が施されたと思われるが、遺構が分布して
いる、または遺物が流入している可能性を残してい
る。当地周辺における工事計画には引き続き慎重
な対応が必要である。
【註】
１）横山成己（2013）「アーチェリー場整備工事に伴う立会調査」，
山口大学埋蔵文化財資料館（編）『山口大学埋蔵文化財資料
館－平成21年度－』，山口
吉田構内（吉田遺跡）の調査
- 39 -
第３節 小串構内（山口大学医学部構内遺跡）の調査
１．医学部附属病院多用途型トリアージスペース整備事業（本体工事）に伴う立会調査
調査地区 小串構内外来診療棟南東側空閑地
調査面積 170㎡
調査期間 令和３年６月10日
調査担当 横山成己
調査結果
令和２年度末に、小串構内外来診療棟南東空閑
地に多用途型トリアージスペースを新営する事業計
画が提出された（図31）。計画地点は、小串構内の
東を南西に流れる真締川に隣接していることから、
氾濫原であり埋蔵文化財が遺存する可能性は低い
と思われたが、小串構内の広範囲において確認さ
れている近世の耕地化に伴う客土の存否を確認す
る必要があることから、令和２年度第５回埋蔵文化
財資料館専門委員会（令和３年３月31日（水）開催）
にて立会調査の実施が諮られ、承認された。
調査の結果、現地表下230㎝まで造成土であるこ
とが確認されたが、その直下に近世の客土である明
青灰色(5PB7/1)砂質シルトが存在することが明らか
となった。不安定な地盤を耕地化するためか、客土
は他地点より厚く設けられており、現状で50㎝以上
の厚みを有することが確認できた。安全確保のた
め、調査は南壁の一部の断面精査にとどめたが、
十分な成果を得るに至った。
小串構内（山口大学医学部構内遺跡）の調査
0 2m
(1/40)
造成土
明青灰色 (5PB7/1) 砂質シルト…近世客土
外来診療棟
第２中央診療棟
第１病棟
真
締
川
0 50m
(1/2000)
図 31　調査区位置図
写真83　調査区南壁土層断面 （西から）図 32　土層断面柱状図
－   －


Yamaguchi University Hospital

Not a member yet

障害学生修学支援ニーズと修学スケジュールの関連性 : 山口大学の事例から

年齢，性別，hTERT，メチル化RUNX3 を含む新しい指標は早期胃癌の診断に有用である

高浸透性型けい酸塩系改質材を用いた火害を受けたコンクリートの補修技術に関する研究

犬のメラノーマにおける低酸素環境下で調節される非コードRNA分子の役割

3分節ゲノムを有するブニヤウイルスを対象としたリバースジェネティクス系の確立および病原性に関与するウイルス遺伝子の特定

国際的視点からみる地方都市港湾の機能転換－再開発・住民参加・交流事業―

総合的な学習の時間の話し合い場面における「協働」の質を高める授業づくり支援に関する研究

都市における自己家畜化 : 結婚を介した「向社会性」の2重相続仮説に関する検討

第2章令和3年度山口大学構内遺跡の調査 - 第3節小串構内（山口大学医学部構内遺跡）の調査

当科におけるENoG（Electroneurography）を施行した顔面神経麻痺症例の検討

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