Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells

RET/PTC1 fusion oncogene is the most common genetic alteration identified to date in thyroid papillary carcinomas (PTC) and represents a good target forsmall interfering RNA (siRNA). Our aim was: i) to target the RET/PTC1 oncogene by siRNAs, ii) to assess the knockdown effects on cell growth and c...

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Datum:	2011
1. Verfasser:	Massade, L.
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Sprache:	English
Veröffentlicht:	Інститут молекулярної біології і генетики НАН України 2011
Schriftenreihe:	Вiopolymers and Cell
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spelling	irk-123456789-1563802019-06-19T01:25:17Z Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells Massade, L. RET/PTC1 fusion oncogene is the most common genetic alteration identified to date in thyroid papillary carcinomas (PTC) and represents a good target forsmall interfering RNA (siRNA). Our aim was: i) to target the RET/PTC1 oncogene by siRNAs, ii) to assess the knockdown effects on cell growth and cell cycle regulation and iii) to vectorize it in order to protect it from degradation. Methods. Human cell lines expressing RET/PTC1 were transfected by siRNA RET/PTC1, inhibition of the oncogene expression was assessed by qRT-PCR and by Western blot. Conjugation of siRNA RET/PTC1 to squalene was performed by coupling it to squalene. In vivo studies are performed in nude mice. Conclusion. In this short com- munication, we report the main published results obtained during last years. Keywords: RET/PTC1, siRNA, thyroid papillary carcinomas. Злитий онкоген RET/PTC1 є найзагальнішою генетичною зміною, ідентифікованою на сьогодні при папілярних ракових захворюваннях щитоподібної залози (PTC); він являє собою гарну мішень для малих інтерферуючих РНК (міРНК). Мета роботи полягала у 1) дії на онкоген RET/PTC1 за посередництвом siРНК; 2) оцінюванні пошкоджуючого впливу на ріст клітин та і регуляцію клітинного циклу; 3) векторизації для захисту від деградації. Методи. Клітинні лінії людини, які експресують RET/PTC1 були трансфековані міРНК RET/PTC1, інгібування експресії даного онкогену аналізували qRT-PCR і вестерн блот. міРНК RET/PTC1 кон’югували зі скваленом . In vivo дослідження проводилися на безтимусних мишах. Висновки. У даному короткому повідомленні представлено основні опубліковані результати, отримані останніми роками. Ключові слова: RET/PTC1, міРНК, папілярна карцинома щитоподібної залози. Слитый онкоген RET/PTC1 является самым общим генетическим изменением, идентифицированным на сегодня при папиллярных раковых заболеваниях щитовидной железы (PTC); он представляет собой хорошую мишень для малых интерферирующих РНК (миРНК). Цель работы состояла в 1) воздействии на онкоген RET/PTC1 посредством миРНК; 2) оценке повреждающего влияния на рост клеток и регуляцию клеточного цикла; 3) векторизации для защиты от деградации. Методы. Клеточные линии человека экспрессирующие RET/PTC1 были трансфецированы миРНКRET/PTC1, ингибирование экспресии данного онкогена анализировалось qRT-PCR и вестерн блоттом. миРНК RET/ PTC1 конъюгировали со скваленом. In vivo исследованя проводились на безтимусны мышах. Выводы. В данном коротком сообщении мы представляем основные опубликованные результаты, полученные в последние годы. Ключевые слова: RET/PTC1, миРНК, папиллярная карцинома щитовидной железы. 2011 Article Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells / L.Massade // Вiopolymers and Cell. — 2011. — Т. 27, № 5. — С. 390-393. — Бібліогр.: 20 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.00012B http://dspace.nbuv.gov.ua/handle/123456789/156380 577.218 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України
institution	Digital Library of Periodicals of National Academy of Sciences of Ukraine
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language	English
description	RET/PTC1 fusion oncogene is the most common genetic alteration identified to date in thyroid papillary carcinomas (PTC) and represents a good target forsmall interfering RNA (siRNA). Our aim was: i) to target the RET/PTC1 oncogene by siRNAs, ii) to assess the knockdown effects on cell growth and cell cycle regulation and iii) to vectorize it in order to protect it from degradation. Methods. Human cell lines expressing RET/PTC1 were transfected by siRNA RET/PTC1, inhibition of the oncogene expression was assessed by qRT-PCR and by Western blot. Conjugation of siRNA RET/PTC1 to squalene was performed by coupling it to squalene. In vivo studies are performed in nude mice. Conclusion. In this short com- munication, we report the main published results obtained during last years. Keywords: RET/PTC1, siRNA, thyroid papillary carcinomas.
format	Article
author	Massade, L.
spellingShingle	Massade, L. Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells Вiopolymers and Cell
author_facet	Massade, L.
author_sort	Massade, L.
title	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells
title_short	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells
title_full	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells
title_fullStr	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells
title_full_unstemmed	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells
title_sort	characterization and vectorization of sirna targeting ret/ptc1 in human papillary thyroid carcinoma cells
publisher	Інститут молекулярної біології і генетики НАН України
publishDate	2011
url	http://dspace.nbuv.gov.ua/handle/123456789/156380
citation_txt	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells / L.Massade // Вiopolymers and Cell. — 2011. — Т. 27, № 5. — С. 390-393. — Бібліогр.: 20 назв. — англ.
series	Вiopolymers and Cell
work_keys_str_mv	AT massadel characterizationandvectorizationofsirnatargetingretptc1inhumanpapillarythyroidcarcinomacells
first_indexed	2025-07-14T06:25:25Z
last_indexed	2025-07-14T06:25:25Z
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fulltext	Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells L. Massade Universite Paris-Sud, UMR 8203, Orsay, F-91405, CNRS, Orsay, F-91405, Institut Gustave Roussy, Villejuif 94805 UMR 8203 CNRS, Institut Gustave Roussy F-94805 Villejuif Cedex, France liliane.massade@igr.fr RET/PTC1 fusion oncogene is the most common genetic alteration identified to date in thyroid papillary carcinomas (PTC) and represents a good target for small interfering RNA (siRNA). Our aim was: i) to target the RET/PTC1 oncogene by siRNAs, ii) to assess the knockdown effects on cell growth and cell cycle regulation and iii) to vectorize it in order to protect it from degradation. Methods. Human cell lines expressing RET/PTC1 were transfected by siRNA RET/PTC1, inhibition of the oncogene expression was assessed by qRT-PCR and by Western blot. Conjugation of siRNA RET/PTC1 to squalene was performed by coupling it to squalene. In vivo studies are performed in nude mice. Conclusion. In this short com- munication, we report the main published results obtained during last years. Keywords: RET/PTC1, siRNA, thyroid papillary carcinomas. Introduction. Cancers due to chromosomal transloca- tions are considered to represent around 20 % of all can- cers [1]. Genomic rearrangements leading to intragenic fusion are mainly found in some types of haematopoie- tic malignancies and sarcomas. They have recently been described also in carcinomas [2, 3]. The mechanism of formation of most of these translocations is still un- clear, except for RET oncogene in papillary thyroid car- cinomas (PTC) where ionizing radiation is described as an important factor [4]. Thus, thousands of people deve- loped thyroid cancers after the Chernobyl catastrophe [5, 6]. The RET/PTC oncogene was isolated almost twenty years ago [7, 8]. RET/PTC is an early event in the process of thyroid carcinogenesis and plays a criti- cal role in the generation of papillary carcinoma [9]. The RET protooncogene codes for a cell membrane re- ceptor tyro sine kinase and has a role in the regulation of cell growth, survival, differentiation and migration [10]. Rearrangement involving the chromosome 10 between RET and a ubiquitous gene leads to the abnormal ex- pression of a chimeric constitutively activated RET pro- tein in follicular cells [11]. To date, 12 different fusion pattern genes have been reported to form at least 17 different RET hybrid oncogenes. The spatial proximity of Ret gene with H4 during thyrocyte interphase can explain the RET/PTC1 formation [12]. This fusion on- cogene is essentially restricted to the papillary histo- type (60–70 %) [13] and to the Hurthle thyroid tumours (58 %) [14] and its incidence increases after radiation exposure. Moreover, the RET/PTC1 fusion oncogene is pre- sent only in the tumour cells and not in the surroun- ding normal cells, this constitutes an area of important research on emerging therapies such as using small in- terfering RNA (siRNA) to target. Therefore, we tar- geted the RET/PTC1 oncogene by siRNAs and asses- sed the knockdown effects on cell growth and cell cycle regulation, then we vectorized it because the biological 390 ISSN 0233–7657. Biopolymers and Cell. 2011. Vol. 27. N 5. P. 390–393  Institute of Molecular Biology and Genetics, NAS of Ukraine, 2011 efficacy of the siRNAs is hampered by their short plas- matic half-life due to poor stability in biological fluids and by their low intracellular penetration due to their highly hydrophilic character [15, 16]. Material and methods. The human TPC-1 cell li- ne that harbours the RET/PTC1 rearrangement was used. A siRNA targeted to H4/RET termed siRNA RET/PTC1 was designed to knockdown RET/PTC1 in the TPC-1 cells. It was transiently transfected in TPC-1 cells using Lipofectamine 2000 transfection reagent. Then, total RNA was extracted and first-strand cDNA was generated with M-MLV (Reverse Transcription), real time PCR Q-RT-PCR was used to assess the knock- down efficiency. Western blot was performed using Ret antibody and β-actin was used as loading control. The siRNA RET/ PTC1 effects on cell cycle growth (MTT tests), cell cyc- le (flow cytometry) and apoptosis (TUNEL method) were studied (Fig. 1). 391 CHARACTERIZATION AND VECTORIZATION OF siRNA TARGETING RET/PTC1 RET/PTC1 B-actin 0.4 0.8 1.2 A B qRT-PCR Western-Blot 1 2 3 Fig. 1. Gene silencing efficiency of siRNA RET/PTC1 in TPC-1 cells: A – the RET/PTC1 mRNA expression was analyzed by Q-RT-PCR for treated cells by siRNA RET/PTC1 (black) or siRNA CT (grey) and compared to untreated cells (white); the bars represent mean ± SD of at least three independent experiments; *significant change compared to untreated cells using ANOVA followed by Bonferroni’s test (p < < 0.001); B – RET/PTC-1 protein level in untransfected and trans- fected cells with siRNA RET/PTC1 or siRNA CT at 50 nM. Proteins were extracted 24 h after transfection and analyzed by Western blot using Ret antibody; β-actin was used as loading control for Western blot; experiments were performed in triplicate.1 – untreated cells; 2 – control siRNA; 3 – RET/PTC1 siRNA. N NN N O O O PO OH O S N O O RN Nanoparticles A B C DMF + HS-siRNA RET/PTC1 RNA Days of treatment 0 5 10 15 20 0 20 40 60 80 100 120 140 1 2 3 N O O Fig. 2. A – chemical structure of the siRNA sense strand 1 and of the squalenoyl activated moieties 2–5 and conjugation of 1 with squalenoyl ma- leimide 5; B – characterization of siRNA-SQ RET/PTC1 NP. Representative images of the siRNA-SQ RET/PTC1 NPs obtained by cryo-electron microscopy, mean diameter = 164 nm; C – antitumor effects of the siRNA-SQ RET/ PTC1 NPs. Curve 1 – saline; 2 – siRNA-CT-SQ NT; 3 – siRET/PTC1-SQ NP. The treatment was performed by intravenous administration until day 10. Arrows correspond to the days of treatment. Five injections were performed for siRNA-SQ RET/ PTC1 or control] NPs at days 0, 2, 4, 7 and 10 at 2.5 mg/kg cumulative dose. ⇓: Mice were sacri- ficed at day 19. The effects of siRNA-SQ RET/PTC1 NPs on tumour growth in nude mice are expressed relatively to tumour volume on day 1 ac- cording to the following formula: tumour volume at day x/tumour volume at day 1. Bars correspond to the standard deviation for five mice. A statistical difference was observed between treatments (p = 0.01) using the ANOVA test followed by Bonferroni test who showed a statistical difference between siRNA-SQ RET/PTC1 NP and untreated tumours (saline), p = 0.013 For vectorization, a non cationic new approach for the delivery of siRNA targeted toward the RET/PTC1 fusion oncogene; it is based on the concept of «squale- noylation», consisting in the bio-conjugation of a drug substance to squalene (SQ), a non ionic and biocom- patible natural lipid [17, 18]. The acyclic isoprenoid chain of squalene has been covalently coupled with siRNA RET/PTC1 at the 3'-terminus of the sense strand via maleimide-sulfhydryl chemistry. Nanoparticles we- re obtained by precipitation in H2O. These nanopartic- les were tested in vivo, on a mice xenografted RET/ PTC1 experimental model (Fig. 2). Results and discussion. By Q-RT-PCR we found that both siRET/PTC1 significantly reduced the RET/ PTC1 mRNA levels by approximately 80 %. MTT as- say showed a significant decrease in the TPC-1 growth rate in siRNA RET/PTC1-treated cells when compared to untreated cells. Cell cycle progression analysis sho- wed a significant increase of the S-phase in siRNAs- treated cells when compared with the untreated cells. Apoptotic cells were detected using TUNEL staining and a fluorescence microscope. Comprehensive counts showed a modest increase in apoptotic index of about 8.4 ± 1.5 % [19]. Then, we «squalenoylated» the siRNA RET/PTC1, remarkably, the linkage of siRNA RET/PTC1 to squale- ne led to amphiphilic molecule that self-organised in H2O as siRNA-SQ RET/PTC1 nanoparticles (NPs). In vivo, on a mice xenografted RET/PTC1, RET/PTC1- SQ NPs were found to inhibit tumour growth and RET/ PTC1 oncogene and oncoprotein expression, after 2.5 mg/kg cumulative dose intravenous injections [20]. Conclusions. The siRNA RET/PTC1 designed is ef- ficient and specific to RET/PTC1 oncogene, which should open new prospects in treatments by siRNAs for PTC or Hurthle thyroid tumours with RET/PTC1 juncti- on. The «squalenoylation» offers a new non cationic pla- te-form for the siRNA delivery. Further pharmacologi- cal assays are needed both on cell cultures and in vivo before to generalize this concept to other nucleic targets. Acknowledgments. This paper summarizes a part of the PhD thesis work of Marie Gilbert-Sirieix (bio- logical part) and of Mouna Raouane (chemical part). The chemical part of the study was done by the staff of Professor Patrick Couvreur and Doctor Didier Desmae- le, UMR 8612 CNRS, laboratoire «Physico-chimie, pharmacotechnie & Biopharmacie», faculte de Pharma- cie, Chatenay-Malabry, France. Л. Мас сад Ефек ти сай ле син гу RET/PTC1 зли то го онко ге ну у кліти нах папіляр ної кар ци но ми щи то подібної за ло зи лю ди ни: ха рак те рис ти ка і век то ри зація міРНК, на прав ле них на RET/PTC1 Ре зю ме Зли тий онко ген RET/PTC1 є на й за гальнішою ге не тич ною зміною, іден тифіко ва ною на сьо годні при папіляр них ра ко вих за хво рю ван - нях щи то подібної за ло зи (PTC); він являє со бою гар ну мішень для ма лих інтер фе ру ю чих РНК (міРНК). Мета ро бо ти по ля га ла у 1) дії на онко ген RET/PTC1 за по се ред ниц твом siРНК; 2) оціню ванні по шкод жу ю чо го впли ву на ріст клітин та і ре гу ляцію клітин но го цик лу; 3) век то ри зації для за хис ту від дег ра дації. Ме то ди. Клітинні лінії лю ди ни, які експре су ють RET/PTC1 були транс фе - ко вані міРНК RET/PTC1, інгібу ван ня експресії дан о го онко ге ну аналізу ва ли qRT-PCR і вес терн блот. міРНК RET/PTC1 кон’югу - ва ли зі сква леном . In vivo досліджен ня про во ди лися на без ти мус - них мишах. Вис нов ки. У да но му ко рот ко му повідом ленні пред став ле но основні опубліко вані ре зуль та ти, от ри мані останніми ро ка ми. Клю чові сло ва: RET/PTC1, міРНК, папіляр на кар ци но ма щи - то подібної за ло зи. Л. Мас сад Эффек ты сай ле син га RET/PTC1 сли то го онко ге на в клет ках па пил ляр ной кар ци но мы щи то вид ной же ле зы че ло ве ка: ха рак те рис ти ка и век то ри за ция миРНК, на прав лен ных на RET/PTC1 Ре зю ме Сли тый онко ген RET/PTC1 яв ля ет ся са мым об щим ге не ти чес ким из ме не ни ем, иден ти фи ци ро ван ным на се го дня при па пил ляр ных ра ко вых за бо ле ва ни ях щи то вид ной же ле зы (PTC); он пред став - ля ет со бой хо ро шую ми шень для ма лых ин тер фе ри ру ю щих РНК (миРНК). Цель ра бо ты со сто я ла в 1) воз де йствии на онко ген RET/PTC1 по сре дством миРНК; 2) оцен ке по вреж да ю ще го вли я - ния на рост кле ток и ре гу ля цию кле точ но го цик ла; 3) век то ри за - ции для за щи ты от дег ра да ции. Ме то ды. Кле точ ные ли нии че ло ве ка экс прес си ру ю щие RET/PTC1 были транс фе ци ро ва ны миРНКRET/PTC1, ин ги би ро ва ние экс пре сии дан но го онко ге на ана ли зи ро ва лось qRT-PCR и вес терн блот том. миРНК RET/ PTC1 конъю ги ро ва ли со сква ле ном. In vivo ис сле до ва ня про во ди - лись на без ти мус ны мы шах. Вы во ды. В дан ном ко рот ком со об - ще нии мы пред став ля ем основ ные опуб ли ко ван ные ре зуль та ты, по лу чен ные в по след ние годы. Клю че вые сло ва: RET/PTC1, миРНК, па пи лляр ная кар ци но ма щи то вид ной же ле зы. REFERENCES 1. Nambiar M., Kari V., Raghavan S. C. Chromosomal translo- cations in cancer // Biochim. Biophys. Acta.–2008.–1786, N 2.– P. 139–152. 2. Teixeira M. R. Recurrent fusion oncogenes in carcinomas // Crit. Rev. Oncog.–2006.–12, N 3–4.–P. 257–271. 392 MASSADE L. 3. Aman P. Fusion genes in solid tumors // Semin. Cancer Biol.– 1999.–9, N 4.–P. 303–318. 4. Jhiang S. M. The RET proto-oncogene in human cancers // Oncogene.–2000.–19, N 49.–P. 5590–5597. 5. Di Cristofaro J., Vasko V., Savchenko V., Cherenko S., Larin A., Ringel M. D., Saji M., Marcy M., Henry J. F., Carayon P., De Micco C. ret/PTC1 and ret/PTC3 in thyroid tumors from Cher- nobyl liquidators: comparison with sporadic tumors from Ukrai- nian and French patients // Endocr. Relat. Cancer.–2005.–12, N 1.–P. 173–183. 6. Nikiforov Y. E. Radiation-induced thyroid cancer: what we have learned from chernobyl // Endocr. Pathol.–2006.–17, N 4.– P. 307–317. 7. Fusco A., Grieco M., Santoro M., Berlingieri M. T., Pilotti S., Pierotti M. A., Della Porta G., Vecchio G. A new oncogene in human thyroid papillary carcinomas and their lymph-nodal me- tastases // Nature.–1987.–328, N 6126.–P. 170–172. 8. Fusco A., Santoro M. 20 years of RET/PTC in thyroid cancer: clinico-pathological correlations // Arq. Bras. Endocrinol. Me- tabol.–2007.–51, N 5.–P. 731–735. 9. Viglietto G., Chiappetta G., Martinez-Tello F. J., Fukunaga F. H., Tallini G., Rigopoulou D., Visconti R., Mastro A., Santoro M., Fusco A. RET/PTC oncogene activation is an early event in thyroid carcinogenesis // Oncogene.–1995.–11, N 6.– P. 1207–1210. 10. Tallini G., Asa S. L. RET oncogene activation in papillary thyro- id carcinoma // Adv. Anat. Pathol.–2001.–8, N 6.–P. 345–354. 11. Santoro M., Melillo R. M., Fusco A. RET/PTC activation in pa- pillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture // Eur. J. Endocrinol.–2006.–155, N 5.–P. 645– 653. 12. Nikiforova M. N., Stringer J. R., Blough R., Medvedovic M., Fa- gin J. A., Nikiforov Y. E. Proximity of chromosomal loci that par- ticipate in radiation-induced rearrangements in human cells // Science.–2000.–290, N 5489.–P. 138–141. 13. Nikiforov Y. E. RET/PTC rearrangement in thyroid tumors // En- docr. Pathol.–2002.–13, N 1.–P. 3–16. 14. Chiappetta G., Toti P., Cetta F., Giuliano A., Pentimalli F., Amendola I., Lazzi S., Monaco M., Mazzuchelli L., Tosi P., San- toro M., Fusco A. The RET/PTC oncogene is frequently acti- vated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions // J. Clin. Endocrinol. Metab.–2002.–87, N 1.–P. 364–369. 15. Brummelkamp T. R., Bernards R., Agami R. A system for stable expression of short interfering RNAs in mammalian cells // Science.–2002.–296, N 5567.–P. 550–553. 16. Bertling W. M., Gareis M., Paspaleeva V., Zimmer A., Kreuter J., Nurnberg E., Harrer P. Use of liposomes, viral capsids, and nanoparticles as DNA carriers // Biotechnol. Appl. Biochem.– 1991.–13, N 3.–P. 390–405. 17. Couvreur P., Reddy L. H., Mangenot S., Poupaert J. H., Des- maele D., Lepetre-Mouelhi S., Pili B., Bourgaux C., Amenitsch H., Ollivon M. Discovery of new hexagonal supramolecular na- nostructures formed by squalenoylation of an anticancer nuc- leoside analogue // Small.–2008.–4, N 2.–P. 247–253. 18. Couvreur P., Stella B., Reddy L. H., Hillaireau H., Dubernet C., Desmaele D., Lepetre-Mouelhi S., Rocco F., Dereuddre- Bosquet N., Clayette P., Rosilio V., Marsaud V., Renoir J. M., Cattel L. Squalenoyl nanomedicines as potential therapeutics // Nano Lett.–2006.–6, N 11.–P. 2544–2548. 19. Gilbert-Sirieix M., Ripoche H., Malvy C., Massaad-Massade L. Effects of silencing RET/PTC1 junction oncogene in human pa- pillary thyroid carcinoma cells // Thyroid.–2010.–20, N 10.– P. 1053–1065. 20. Raouane M., Desmaele D., Gilbert-Sirieix M., Gueutin C., Zou- hiri F., Bourgaux C., Lepeltier E., Gref R., Ben Salah R., Clay- man G., Massaad-Massade L., Couvreur P. Synthesis, characte- rization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma // J. Med. Chem.–2011.–54, N 12.–P. 4067–4076. UDC 577.218 Received 20.06.11 393 CHARACTERIZATION AND VECTORIZATION OF siRNA TARGETING RET/PTC1

Characterization and vectorization of siRNA targeting RET/PTC1 in human papillary thyroid carcinoma cells

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