Vloga dolge nekodirajoče rna inc-fanci-2 pri raku glave in vratu

diplomsko delo univerzitetnega študijskega programa I. stopnje

Jure Šuster (Author), Uroš Potočnik (Mentor), Tomaž Büdefeld (Co-mentor), Boštjan Lanišnik (Co-mentor)

Abstract

Rak glave in vratu (angl. Head and Neck Cancer, HNC) predstavlja raznoliko skupino rakov, med katere uvrščamo rake ustne votline in ustnic, nosa in obnosne votline, grla, žrela ter žlez slinavk. Po ocenah iz leta 2016 je bilo na svetu evidentiranih 4,1 miliona vseh primerov HNC, kar ga uvršča na sedmo mesto najpogostejših rakov. Letno zaradi HNC umre okoli 500.000 ljudi. Najpogostejši dejavnik tveganja za nastanek HNC sta kajenje in prekomerno uživanje alkohola. Vse pogosteje pa nastanek HNC, predvsem rake srednjega dela žrela, povezujejo z okužbo z onkogenimi serotipi človeških papilomavirusov (HPV). Nedavno nazaj so ugotovili, da okužba s HPV16 poviša izražanje dolge nekodirajoče RNA (lnc RNA) lnc-FANCI-2 pri raku na materničnem vratu. Da bi ugotovili, ali je mehanizem onkogenega delovanja HPV16 ohranjen med raki materničnega vratu in HNC, smo v diplomski nalogi z metodo RT-qPCR proučili izražanje prepisov lnc-FANCI-2 dA1 in dA2 in lokusa MIR9-3HG, ki zraven izooblik lnc-FANCI-2 kodira še druge nekodirajoče RNA, pri bolnikih s ploščato celičnim karcinomom glave in vratu (angl. Head and Neck Squamous Cell Carcinoma, HNSCC), okuženih s HPV16. Skupno gledano je bilo Izražanje MIR9-3HG višje (p< 0,01) v tumorjih kot zdravem tkivu, razlika pa se je ohranila (p< 0,05) tudi pri rakih žrela. HPV16 (+) tumorji so kazali nižje (p< 0,05) izražanje MIR9-3HG v primerjavi s HPV16 (-) tumorji, kar kaže, da okužba s HPV16 zavira izražanje lokusa MIR9-3HG. Za razliko od okužbe s HPV16 pa vpliva dejavnikov tveganja kajenja in uživanja alkohola na izražanje MIR9-3HG nismo ugotovili. Izražanje MIR9-3HG se ni razlikovalo med tumorji s perivaskularno, perinevralno ali limfovaskularno invazijo in tumorji brez invazije. Razširjeni tumorji z zasevki v lokalnih bezgavkah (cN1+, pN1+) so kazali nižje izražanje MIR9-3HG v primerjavi s tumorji brez zasevkov (cN0, pN0), vendar razlika ni dosegla statistične značilnosti. Izražanje MIR9-3HG se ni razlikovalo glede na velikost tumorja (cT1-cT4, pT1-pT4). Izražanja prepisov lnc-FANCI-2 dA1 in dA2 na proučevanem vzorcu bolnikov nismo potrdili. Rezultati naše naloge kažejo na vlogo lokusa MIR9-3HG pri nastanku HNSCC v prisotnsoti okužbe s HPV16. Ali pri tem sodelujejo tudi izooblike lnc-FANCI-2 ni znano in bo njihovo vlogo v tumorigenezi HNSCC v nadaljevanju potrebno še proučiti.

Keywords

rak glave in vratu;MIR9-3HG;lnc FANCI-2;HPV16;RT-qPCR;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2023
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[J. Šuster]
UDC:	616-006:611.31(043.2)
COBISS:	171982851
Views:	22
Downloads:	3
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Role of long non-coding rna inc-fanci-2 in head and neck cancer
Secondary abstract:	Head and Neck Cancer (HNC) represents a diverse group of cancers that include cancers of the oral cavity and lips, nasal and paranasal cavities, larynx, pharynx and salivary glands. According to estimates from 2016, there were 4.1 million total cases of HNC worldwide, making it the seventh most common cancer. Approximately 500,000 people die from HNC each year. The most common risk factors for HNC are smoking and excessive alcohol consumption. However, HNC, particularly oropharyngeal cancers, are increasingly associated with infection with oncogenic human papillomavirus (HPV) serotypes. Recently, HPV16 infection was found to increase the expression of the long non-coding RNA (lnc RNA) lnc-FANCI-2 in cervical cancer. To determine whether the mechanism of oncogenic action of HPV16 is conserved between cervical cancer and HNC, in the present study, we investigated the expression of the lnc-FANCI-2 dA1 and dA2 transcripts and the MIR9-3HG locus, which encodes other non-coding RNAs in addition to the lnc-FANCI-2 isoforms, in HPV16-infected patients with head and neck squamous cell carcinoma (HNSCC) using RT-qPCR. Overall, MIR9-3HG expression was higher (p<0.01) in tumours than in normal tissue, and the difference was conserved (p<0.05) in oropharyngeal cancers. HPV16 (+) tumours showed lower (p<0.05) MIR9-3HG expression compared to HPV16 (-) tumours, suggesting that HPV16 infection suppresses MIR9-3HG expression. Unlike HPV16 infection, we found no effect of smoking and alcohol consumption on MIR9-3HG expression. MIR9-3HG expression did not differ between tumours with perivascular, perineural or lymphovascular invasion and noninvaded tumours. Tumours with local lymph node metastasis (cN1+, pN1+) showed lower MIR9-3HG expression than tumours without metastasis (cN0, pN0), but the difference did not reach statistical significance. There was no difference in MIR9-3HG expression between tumour sizes (cT1-cT4, pT1-pT4). Expression of lnc-FANCI-2 dA1 and dA2 isoforms was not confirmed in the patient sample studied. Our results suggest a role for the MIR9-3HG in HPV16 (+)-related HNSCC. Whether this is also the case for the lnc-FANCI-2 isoforms is unknown and requires further study.
Secondary keywords:	head and neck cancer;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo, Kemijsko inženirstvo
Pages:	1 spletni vir (1 datoteka PDF (X, 48 f.))
ID:	19859657