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5’tiRNA-Pro-TGG,a novel tRNA halve,promotes oncogenesis in sessile serrated lesions and serrated pathway of colorectal cancer

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World Journal of Gastrointestinal Oncology 2023年第6期15卷 1005-1018页

作者： Xin-Yuan Wang Yu-Jie Zhou Hai-Ying Chen Jin-Nan Chen Shan-Shan Chen Hui-Min Chen Xiao-Bo Li Division of Gastroenterology and Hepatology Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200000China Department of Spleen and Stomach and Rheumatology Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

BACKGROUND Transfer RNA(tRNA)-derived small RNAs(tsRNAs)are small fragments that form when tRNAs *** halves(tiRNAs),a subcategory of tsRNA,are involved in the oncogenic processes of many ***,their specific role in sessile serrated lesions(SSLs),a precancerous lesion often observed in the colon,has not yet been *** To identify SSL-related tiRNAs and their potential role in the development of SSLs and serrated pathway of colorectal cancer(CRC).METHODS Small-RNA sequencing was conducted in paired SSLs and their adjacent normal control(NC)*** expression levels of five SSL-related tiRNAs were validated by q-polymerase chain *** counting kit-8 and wound healing assays were performed to detect cell proliferation and *** target genes and sites of tiRNA-1:33-Pro-TGG-1(5′tiRNA-Pro-TGG)were predicted by TargetScan and miRanda ***-associated and immune-related pathways were analyzed by single-sample gene set enrichment *** analyses were performed to establish the roles of 5′tiRNA-Pro-TGG based on the target *** In total,we found 52 upregulated tsRNAs and 28 downregulated tsRNAs in SSLs compared to *** expression levels of tiRNA-1:33-Gly-CCC-2,tiRNA-1:33-Pro-TGG-1,and tiRNA-1:34-Thr-TGT-4-M25′tiRNAs were higher in SSLs than those in NC,while that of 5′tiRNA-Pro-TGG was associated with the size of *** was demonstrated that 5′tiRNAPro-TGG promoted cell proliferation and migration of RKO cell in ***,heparanase 2(HPSE2)was identified as a potential target gene of 5′*** lower expression was associated with a worse prognosis in ***,lower expression of HPSE2 was observed in SSLs compared to normal controls or conventional adenomas and in BRAF-mutant CRC compared to BRAF-wild *** analyses revealed that its low expression was associated with a low interferonγresponse and also with many metabolic pathways such as riboflavin,retinol,and cy

关键词： Noncoding RNA tRNA halves Sessile serrated lesions Colon cancer serrated pathway

MicroRNA-31 expression in colorectal serrated pathway progression

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World Journal of Gastroenterology 2014年第34期20卷 12346-12349页

作者： Hironori Aoki Katsuhiko Nosho Hisayoshi Igarashi Miki Ito Kei Mitsuhashi Takafumi Naito Eiichiro Yamamoto Tokuma Tanuma Masafumi Nomura Hiroyuki Maguchi Toshiya Shinohara Hiromu Suzuki Hiroyuki Yamamoto Yasuhisa Shinomura Center for Gastroenterology Teine-Keijinkai HospitalSapporo 006-0811Japan Department of Gastroenterology Rheumatology and Clinical ImmunologySapporo Medical University School of MedicineSapporo 060-8543Japan Department of Gastroenterology Rheumatology andClinical ImmunologySapporo Medical University School of MedicineSapporo 060-8543Japan Department of Pathology Teine-KeijinkaiHospitalSapporo 006-0811Japan Department of Molecular Biology SapporoMedical University School of MedicineSapporo 060-8543Japan Division of Gastroenterology and Hepatology Department of Internal MedicineSt. Marianna University School of MedicineKawasaki 216-8511Japan

MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in ***,high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps(HPs).These results suggest that miR-31 may contribute to the progression of serrated *** a follow-up colonoscopy,we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated *** specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP *** miR-31 expression was observed in the carcinoma component(57-fold increase)and the HP component(8-fold increase)compared with the paired normal mucosa,suggesting that miR-31 may be one of the key molecules in serrated pathway progression.

关键词： BRAF Colorectal carcinoma MicroRNA-31 MLH1 microsatellite instability serrated pathway

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

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World Journal of Gastroenterology 2020年第42期26卷 6556-6571页

作者： Milena Peruhova Monika Peshevska-Sekulovska Boris Krastev Gabriela Panayotova Viktoriya Georgieva Rossitza Konakchieva Georgi Nikolaev Tsvetelina Veselinova Velikova Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Clinical Oncology MHAT Hospital for Women Health NadezhdaSofia 1330Bulgaria Faculty of Biology Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria

In the last two decades,the vision of a unique carcinogenesis model for colorectal carcinoma(CRC)has completely *** addition to the adenoma to carcinoma transition,colorectal carcinogenesis can also occur via the serrated *** non-coding RNA,known as microRNAs(miRNAs),were also shown to be involved in progression towards ***,increased expression of certain miRNAs in premalignant sessile serrated lesions(SSLs)was found,emphasizing their role in the serrated pathway progression towards colon *** miRNAs function as post-transcriptional gene regulators,they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs *** this review,we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated *** focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway,which remains unstudied.

关键词： MicroRNA serrated pathway Carcinogenesis Colorectal carcinoma Sessile serrated lesions Adenocarcinoma

serrated polyposis syndrome:Molecular,pathological and clinical aspects

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World Journal of Gastroenterology 2012年第20期18卷 2452-2461页

作者： Carla Guarinos Cristina Sánchez-Fortún María Rodríguez-Soler Cristina Alenda Artemio Payá Rodrigo Jover Research Unit Hospital General Universitario de Alicante03010 AlicanteSpain Unidad de Gastroenterología Hospital General Universitario de Alicante03010 AlicanteSpain Department of Pathology Hospital General Universitario de Alicante03010 AlicanteSpain

Hyperplastic polyps have traditionally been considered not to have malignant *** pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this *** recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found thatthis pathway accounts for only approximately 70%-80% of colorectal cancer(CRC)*** majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite *** mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF *** polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the *** characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified *** with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been *** criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal *** this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

关键词： Colorectal cancer Hyperplastic polyps CpG island methylator phenotype serrated polyposis serrated pathway

IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

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World Journal of Gastroenterology 2014年第29期20卷 10050-10061页

作者： Takafumi Naito Katsuhiko Nosho Miki Ito Hisayoshi Igarashi Kei Mitsuhashi Shinji Yoshii Hironori Aoki Masafumi Nomura Yasutaka Sukawa Eiichiro Yamamoto Yasushi Adachi Hiroaki Takahashi Masao Hosokawa Masahiro Fujita Toshinao Takenouchi Reo Maruyama Hiromu Suzuki Yoshifumi Baba Kohzoh Imai Hiroyuki Yamamoto Shuji Ogino Yasuhisa Shinomura Department of Gastroenterology Rheumatology and Clinical ImmunologySapporo Medical University School of Medicine Department of Gastroenterology Keiyukai Sapporo Hospital Center for Gastroenterology Teine-Keijinkai Hospital Department of Medical Oncolo-gy Dana-Farber Cancer InstituteBostonMA 02115United States Department of Surgery Keiyukai SapporoHospital Department of Pathology Keiyukai Sapporo Hospital Department of Molecular Biology Sapporo Medical University School of Medicine Department of Gastroenterological Surgery Graduate School of Medical ScienceKumamoto University Division of Cancer Research The Institute of Medical ScienceThe University of Tokyo Division of Gastroenterology and Hepatology Department of Internal MedicineSt.Marianna University School of Medicine

AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.

关键词： BRAF Colon polyp Colorectal neoplasia Colorectum Genome Insulin-like growth factor Long interspersed nucleotide element-1 Microsatellite instability serrated pathway

Missed colorectal cancers in a fecal immunochemical test-based screening program: Molecular profiling of interval carcinomas

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World Journal of Gastrointestinal Oncology 2022年第11期14卷 2195-2207页

作者： Manon van der Vlugt Beatriz Carvalho Joelle Fliers Nahid Montazeri Christian Rausch Esmée J Grobbee Manon van Engeland Manon C W Spaander Gerrit A Meijer Evelien Dekker Department of Gastroenterology and Hepatology Amsterdam University Medical CenterAmsterdam 1105 AZNetherlands Department of Pathology Netherlands Cancer InstituteAmsterdam 1066 CXNetherlands Biostatistics Unit Department of Gastroenterology and HepatologyAmsterdam University Medical CenterAmsterdam 1105 AZNetherlands Department of Gastroenterology and Hepatology Erasmus MC University Medical CenterRotterdam 3015 CNNetherlands Department of Pathology GROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands

BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important *** of the molecular make-up of these missed lesions could facilitate more accurate detection of all(precursor)*** To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT[screen-detected CRCs(SD-CRCs)].METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio,resulting in 27 FIT-interval CRC and 54 *** analyses included microsatellite instability(MSI),CpG island methylator phenotype(CIMP),DNA sequence mutations and copy number alterations(CNAs).RESULTS Although no significant differences were reached,FIT-interval CRCs were more often CIMP positive and MSI positive(33%CIMP in FIT-interval CRCs vs 21%in SD-CRCs(P=0.274);19%MSI in FIT-interval CRCs vs 12%in SD-CRCs(P=0.469)),and showed more often serrated pathway associated features such as BRAF(30%vs 12%,P=0.090)and PTEN(15%vs 2.4%,P=0.063)*** mutations,a classic feature of the adenoma-carcinoma-sequence,were more abundant in SD-CRCs(68%vs 40%in FIT-interval CRCs P=0.035).Regarding CNAs differences between the two groups;FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3(P=0.009),and more often gains at 20p13-p12.1(P=0.039).CONCLUSION serrated pathway associated molecular features seem to be more common in FIT-interval CRCs,while classic adenoma carcinoma pathway associated molecular features seem to be more common in *** indicates that proximal serrated lesions may be overrepresented among FITinterval CRCs.

关键词： Fecal immunochemical test-interval colorectal cancer Mutation analysis Colorectal cancer screening serrated pathway Adenoma-carcinoma pathway

From traditional serrated adenoma to tubulovillous adenoma and beyond

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World Journal of Gastrointestinal Oncology 2016年第12期8卷 805-809页

作者： Sangeetha N Kalimuthu Adeline Chelliah Runjan Chetty Department of Pathology Laboratory Medicine ProgramUniversity Health Network and University of Toronto

It is well established that colorectal cancer develops from a series of precursor epithelial polyps, including tubular adenomas, villous/tubulovillous adenomas (VA/TVA), sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA). Of these, TSAs are least common and account for only 5% of all serrated polyps. TSAs are characterised by the presence of a “pinecone-like” architecture, granular eosinophilic cytoplasm, luminal serrations, ectopic crypt foci (ECF) and elongated, pencillate nuclei. However, the distinct slit-like luminal serrations, reminiscent of small bowel mucosa, appear to be the most unique and reproducible feature to distinguish TSAs from other polyps. There is a contention that TSAs are not inherently dysplastic and that the majority do not show cytological atypia. Two types of dysplasia are associated with TSA. serrated dysplasia is less well recognised and less commonly encountered than adenomatous dysplasia. In addition, it is now becoming increasingly evident that TSAs can be admixed with HP, SSA and VA/TVA. At a genetic level, polyps may switch phenotype as they accumulate genetic changes, evolving from a serrated pathway to a more conventional one, which could be the basis for a spectrum theory starting out with a TSA with serration and ECF evolving into a TSA with conventional dysplasia and, eventually, to a well-developed conventional adenoma. Nevertheless, there is an exigency for future studies to provide further illumination and bridge the gaps in our present understanding.

关键词： serrated polyps Traditional serrated adenoma Tubullovilous adenoma serrated pathway Fusion pathways