Overview of miRNAs for the non-invasive diagnosis of endometriosis: evidence, challenges and strategies. A systematic review

Monnaka, Vitor Ulisses; Hernandes, Camila; Heller, Debora; Podgaec, Sérgio

doi:10.31744/einstein_journal/2021RW5704

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Sumário

REVIEW • Einstein (São Paulo) 19 • 2021 • https://doi.org/10.31744/einstein_journal/2021RW5704 copy

Overview of miRNAs for the non-invasive diagnosis of endometriosis: evidence, challenges and strategies. A systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective

The aim of the study was to assess the evidence on miRNAs as biomarkers for the diagnosis of endometriosis, as well as to provide insights into the challenges and strategies associated with the use of these molecules as accessible tools in clinical practice.

Methods

Systematic review conducted on PubMed^®, Latin American and Caribbean Health Sciences Literature (LILACS), MEDLINE^® and Web of Science databases using the search terms endometriosis (all fields) AND miRNA (all fields), evaluating all publication up to May 2019.

Results

Most miRNAs found to be dysregulated in this study were harvested from tissue samples, which precludes their use as a non-invasive diagnostic test. However, differential expression of 62 miRNAs was reported in samples that may be used for non-invasive diagnosis of endometriosis, such as blood, serum and plasma.

Conclusion

Despite the identification of several candidates, studies are investigatory in nature and have been conducted with small number of samples. Also, no particular miRNA has been validated for diagnostic purposes so far. Studies based primarily on biological samples and applicable to translational research are warranted. Large databases comprising information on sample type and the use of saliva and vaginal fluid for miRNAs identification may prove essential to overcome current barriers to diagnosis of endometriosis.

Biomarkers; Saliva; Serum; Vaginal fluid; Body fluids banks; MicroRNAs; Endometriosis/diagnosis

miRNA	Regulation	Endometriosis n	Control n	References
miR-126	DR	31	27	Liu et al.⁽²⁰⁾
miR-1281	UR	38	38	Yang et al.⁽²¹⁾
miR-142-5p	UR	38	38	Yang et al.⁽²¹⁾
miR-145	UR	11	22	Zheng et al.⁽²²⁾
miR-146a-5p	UR	38	38	Yang et al.⁽²¹⁾
miR-183-5p	DR	N/A	N/A	Shi et al.⁽²³⁾
miR-199a	DR	12	12	Dai et al.⁽²⁴⁾
miR-202-3p	DR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-204	DR	38	9	Haikalis et al.⁽²⁶⁾
miR-29c	DR	20	10	Long et al.⁽²⁷⁾
miR-30d-5p	UR	21	25	Laudanski et al.⁽²⁸⁾
miR-3152-5p	UR	21	25	Laudanski et al.⁽²⁸⁾
miR-34b	DR	4	3	Burney et al.⁽²⁹⁾
miR-34c-5p	DR	4	3	Burney et al.⁽²⁹⁾
miR-424-5p	DR	51	32	Braza-Boils et al.⁽²⁵⁾
miR-4634	UR	38	38	Yang et al.⁽²¹⁾
miR-483-5p	DR	21	25	Laudanski et al.⁽³⁰⁾
miR-5187-3p	UR	21	25	Laudansk et al.⁽²⁸⁾
miR-543	DR	38	38	Yang et al.⁽²¹⁾
miR-556-3p	DR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-629*	DR	21	25	Laudanski et al.⁽³⁰⁾
miR-9	DR	4	3	Burney et al.⁽²⁹⁾
miR-940	UR	38	38	Yang et al.⁽²¹⁾

miRNA	Regulation	Endometriosis n	Control n	References
let-7g	UR	N/A	N/A	Wright et al.⁽³¹⁾
miR-100	UR	N/A	N/A	Wright et al.⁽³¹⁾
miR-1304-3p	UR	14	10	Xu et al.⁽³²⁾
miR-133a-3p	UR	33	17	Braicu et al.⁽³³⁾
miR-138	UR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-141	UR	22	24	Saare et al.⁽³⁴⁾
miR-143	UR	11	22	Zheng et al.⁽²²⁾
miR-145	UR	11	22	Zheng et al.⁽²²⁾
miR-148a	UR	N/A	N/A	Wright et al.⁽³¹⁾
miR-183-5p	DR	N/A	N/A	Shi et al.⁽²³⁾
miR-191	UR	12	12	Dong et al.⁽³⁵⁾
miR-199a	DR	12	12	Dai et al.⁽²⁴⁾
miR-200a	UR	22	24	Saare et al.⁽³⁴⁾
miR-200b	UR	22	24	Saare et al.⁽³⁴⁾
miR-200c	DR	27	12	Liang et al.⁽³⁶⁾
miR-202-3p	UR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-205-5p	DR	14	10	Xu et al.⁽³²⁾
miR-20a	UR	40	20	Zhao et al.⁽³⁷⁾
miR-21-3p	UR	7	7	Qi et al.⁽³⁸⁾
miR-223-3p	UR	7	7	Qi et al.⁽³⁸⁾
miR-29a	UR	N/A	N/A	Wright et al.⁽³¹⁾
miR-29c	DR	20	10	Long et al.⁽²⁷⁾
miR-29c	UR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-29c	UR	15	11	Joshi et al.⁽³⁹⁾
miR-325	UR	33	17	Braicu et al.⁽³³⁾
miR-33b	DR	20	15	Yang et al.⁽⁴⁰⁾
miR-34c	UR	22	24	Saare et al.⁽³⁴⁾
miR-3663-3p	UR	7	7	Qi et al.⁽³⁸⁾
miR-3684	UR	14	10	Xu et al.⁽³²⁾
miR-373-3p	UR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-3935	DR	14	10	Xu et al.⁽³²⁾
miR-411-5p	UR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-4427	DR	14	10	Xu et al.⁽³²⁾
miR-449a	UR	22	24	Saare et al.⁽³⁴⁾
miR-450a-5p	DR	7	7	Qi et al.⁽³⁸⁾
miR-451	UR	30	0	Graham et al.⁽⁴¹⁾
miR-4683	UR	14	10	Xu et al.⁽³²⁾
miR-492	UR	33	17	Braicu et al.⁽³³⁾
miR-494-5p	UR	14	10	Xu et al.⁽³²⁾
miR-503-5p	DR	7	7	Qi et al.⁽³⁸⁾
miR-520e	UR	33	17	Braicu et al.⁽³³⁾
miR-544b	UR	14	10	Xu et al.⁽³²⁾
miR-5481	DR	N/A	N/A	Wright et al.⁽³¹⁾
miR-652-5p	DR	14	10	Xu et al.⁽³²⁾
miR-6747-3p	UR	14	10	Xu et al.⁽³²⁾

miRNA	Regulation	Endometriosis n	Control n	References
miR-106a-5p	DR	22	0	Zhao et al.⁽⁴²⁾
miR-106b-5p	UR	32	19	Yang et al.⁽⁴³⁾
miR-10a	DR	38	38	Haikalis et al.⁽²⁶⁾
miR-125a	UR	58	38	Ramón et al.⁽⁴⁴⁾
miR-126	DR	31	27	Liu et al.⁽²⁰⁾
miR-126	UR	8	N/A	Ohlsson Teague et al.⁽⁴⁵⁾
miR-141	DR	8	N/A	Ohlsson Teague et al.⁽⁴⁵⁾
miR-145	UR	8	N/A	Ohlsson Teague et al.⁽⁴⁵⁾
miR-145-5p	UR	32	19	Yang et al.⁽⁴³⁾
miR-146a-5p	DR	32	19	Yang et al.⁽⁴³⁾
miR-15a-5p	DR	32	19	Yang et al.⁽⁴³⁾
miR-16-5p	UR	32	19	Yang et al.⁽⁴³⁾
miR-182	DR	16	N/A	Filigheddu et al.⁽⁴⁶⁾
miR-182-5p	DR	22	0	Zhao et al.⁽⁴²⁾
miR-19b-1-5p	DR	32	19	Yang et al.⁽⁴³⁾
miR-200a	DR	16	N/A	Filigheddu et al.⁽⁴⁶⁾
miR-200a-3p	DR	22	0	Zhao et al.⁽⁴²⁾
miR-200b	DR	16	N/A	Filigheddu et al.⁽⁴⁶⁾
miR-200b	DR	8	N/A	Ohlsson Teague et al.⁽⁴⁵⁾
miR-200b	DR	32	19	Yang et al.⁽⁴³⁾
miR-200c	DR	16	N/A	Filigheddu et al.⁽⁴⁶⁾
miR-200c	DR	32	19	Yang et al.⁽⁴³⁾
miR-202	UR	16	N/A	Filigheddu et al.⁽⁴⁶⁾
miR-21	DR	38	38	Haikalis et al.⁽²⁶⁾
miR-222	UR	58	38	Ramón et al.⁽⁴⁴⁾
miR-34c	DR	22	0	Zhao et al.⁽⁴²⁾
miR-424	DR	8	N/A	Ohlsson Teague et al.⁽⁴⁵⁾
miR-424	DR	38	38	Haikalis et al.⁽²⁶⁾
miR-449b	DR	51	32	Braza-Boïls et al.⁽²⁵⁾
miR-449b	DR	22	0	Zhao et al.⁽⁴²⁾
miR-451a	UR	41	40	Nothnick et al.⁽⁴⁷⁾
miR-615	UR	22	0	Zhao et al.⁽⁴²⁾
miR-9	DR	38	38	Haikalis et al.⁽²⁶⁾
miR-99a	UR	8	N/A	Ohlsson Teague et al.⁽⁴⁵⁾

miRNA	Regulation	Endometriosis n	Control n	References
let-7b	DR	24	24	Cho et al.⁽⁴⁸⁾
let-7b-5p	DR	20	26	Nematian et al.⁽⁴⁹⁾
miR-122	UR	60	25	Wang et al.⁽¹⁹⁾
miR-122	UR	45	35	Maged et al.⁽⁵⁰⁾
miR-125b-5p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-125b	UR	20	26	Nematian et al.⁽⁴⁹⁾
miR-127-3p	DR	30	20	Wang et al.⁽⁵²⁾
miR-135a	DR	24	24	Cosar et al.⁽⁵¹⁾
miR-141	DR	60	25	Wang et al.⁽¹⁹⁾
miR-143-3p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-145	DR	60	25	Wang et al.⁽¹⁹⁾
miR-145-5p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-150-5p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-15b-5p	DR	30	20	Wang et al.⁽⁵²⁾
miR-17	DR	80	60	Wang et al.⁽⁵³⁾
miR-185-5p	UR	30	20	Wang et al.⁽⁵²⁾
miR-18a-5p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-191	UR	12	12	Dong et al.⁽³⁵⁾
miR-199a	UR	60	25	Wang et al.⁽¹⁹⁾
miR-199a	UR	45	35	Maged et al.⁽⁵⁰⁾
miR-199a-5p	DR	40	25	Hsu et al.⁽⁵⁴⁾
miR-20a-5p	DR	30	20	Wang et al.⁽⁵²⁾
miR-30c-5p	DR	30	20	Wang et al.⁽⁵²⁾
miR-342-3p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-3613-5p	DR	24	24	Cosar et al.⁽⁵¹⁾
miR-370	DR	20	26	Hu et al.⁽⁵⁵⁾
miR-424-3p	UR	30	20	Wang et al.⁽⁵²⁾
miR-451a	UR	41	40	Nothnick et al.⁽⁴⁷⁾
miR-451a	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-500a-3p	UR	24	24	Cosar et al.⁽⁵¹⁾
miR-542-3p	DR	60	25	Wang et al.⁽¹⁹⁾
miR-6755-3p	DR	24	24	Cosar et al.⁽⁵¹⁾
miR-9	DR	60	25	Wang et al.⁽¹⁹⁾
miR-99b-5p	DR	30	20	Wang et al.⁽⁵²⁾

miRNA	Regulation	Endometriosis n	Control n	References
miR-139	DR	80	39	Nisenblat et al.⁽⁵⁶⁾
miR-141	DR	61	65	Rekker et al.⁽⁵⁷⁾
miR-145	UR	55	23	Bashti et al.⁽⁵⁸⁾
miR-154-5p	DR	51	41	Pateisky et al.⁽⁵⁹⁾
miR-155	DR	80	39	Nisenblat et al.⁽⁵⁶⁾
miR-16	UR	33	20	Suryawanshi et al.⁽⁶⁰⁾
miR-17-5p	DR	23	23	Jia et al.⁽⁶¹⁾
miR-191	UR	33	20	Suryawanshi et al.⁽⁶⁰⁾
miR-195	UR	33	20	Suryawanshi et al.⁽⁶⁰⁾
miR-196b	DR	51	41	Pateisky et al.⁽⁵⁹⁾
miR-200a	DR	61	65	Rekker et al.⁽⁵⁷⁾
miR-200b	DR	61	65	Rekker et al.⁽⁵⁷⁾
miR-20a	DR	23	23	Jia et al.⁽⁶¹⁾
miR-22	DR	23	23	Jia et al.⁽⁶¹⁾
miR-31	DR	55	23	Bashti et al.⁽⁵⁸⁾
miR-33a	UR	51	41	Pateisky et al.⁽⁵⁹⁾
miR-378a	DR	51	41	Pateisky et al.⁽⁵⁹⁾
miR-574	DR	80	39	Nisenblat et al.⁽⁵⁶⁾

miRNA	Regulation	Endometriosis n	Control n	References
let-3c	DR	4	3	Azmy et al.⁽⁶²⁾
let-7e	DR	4	3	Azmy et al.⁽⁶²⁾
let-7f	DR	5	3	Azmy et al.⁽⁶²⁾
let-7g	DR	4	3	Azmy et al.⁽⁶²⁾
miR-103	DR	4	3	Azmy et al.⁽⁶²⁾
miR-106b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-125a-5p	DR	4	3	Azmy et al.⁽⁶²⁾
miR-126	DR	4	3	Azmy et al.⁽⁶²⁾
miR-15b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-16	DR	4	3	Azmy et al.⁽⁶²⁾
miR-17	DR	4	3	Azmy et al.⁽⁶²⁾
miR-181b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-18a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-194	DR	4	3	Azmy et al.⁽⁶²⁾
miR-195	DR	4	3	Azmy et al.⁽⁶²⁾
miR-19a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-19b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-20a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-21	DR	4	3	Azmy et al.⁽⁶²⁾
miR-22	DR	4	3	Azmy et al.⁽⁶²⁾
miR-26a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-26b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-27a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-27b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-30a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-374a	DR	4	3	Azmy et al.⁽⁶²⁾
miR-374b	DR	4	3	Azmy et al.⁽⁶²⁾
miR-424	DR	4	3	Azmy et al.⁽⁶²⁾
miR-7	DR	4	3	Azmy et al.⁽⁶²⁾
miR-93	DR	4	3	Azmy et al.⁽⁶²⁾

miRNA	Regulation	Endometriosis n	Control n	References
miR-106b-3p	UR	126	45	Marí-Alexandre et al.⁽⁶³⁾
miR-122	UR	45	35	Maged et al.⁽⁵⁰⁾
miR-130b	UR	6	3	Chen et al.⁽⁶⁴⁾
miR-199a	UR	45	35	Maged et al.⁽⁵⁰⁾
miR-451a	UR	126	45	Marí-Alexandre et al.⁽⁶³⁾
miR-486-5p	UR	126	45	Marí-Alexandre et al.⁽⁶³⁾

Total	EU versus EN	EC versus EN	EC versus EU	Plasma	Serum	Blood	PF	References
6	miR-145	miR-145	miR-145	miR-145	miR-145			Wang et al.,⁽¹⁹⁾ Zheng et al.,⁽²²⁾ Yang et al.,⁽⁴³⁾ Ohlsson Teague et al.,⁽⁴⁵⁾ Cosar et al.⁽⁵¹⁾ and Bashti et al.⁽⁵⁸⁾
5		miR-200b	miR-200b	miR-200b				Saare et al.,⁽³⁴⁾ Yang et al.,⁽⁴³⁾ Ohlsson Teague et al.,⁽⁴⁵⁾ Filigheddu et al.⁽⁴⁶⁾ and Rekker et al.⁽⁵⁷⁾
5	miR-424		miR-424		miR-424	miR-424		Braza-Boils et al.,⁽²⁵⁾ Haikalis et al.,⁽²⁶⁾ Ohlsson Teague et al.,⁽⁴⁵⁾ Wang et al.⁽⁵²⁾ and Azmy et al.⁽⁶²⁾
4	miR-199a	miR-199a			miR-199a		miR-199a	Wang et al.,⁽¹⁹⁾ Dai et al.,⁽²⁴⁾ Maged et al.⁽⁵⁰⁾ and Hsu et al.⁽⁵⁴⁾
4		miR-141	miR-141	miR-141	miR-141			Wang et al.,⁽¹⁹⁾ Saare et al.,⁽³⁴⁾ Ohlsson Teague et al.⁽⁴⁵⁾ and Rekker et al.⁽⁵⁷⁾
4		miR-20a		miR-20a	miR-20a	miR-20a		Zhao et al.,⁽³⁷⁾ Wang et al.,⁽⁵²⁾ Jia et al.⁽⁶¹⁾ and Azmy et al.⁽⁶²⁾
4		miR-200a	miR-200a	miR-200a				Saare et al.,⁽³⁴⁾ Zhao et al.,⁽⁴²⁾ Filigheddu et al.⁽⁴⁶⁾ and Rekker et al.⁽⁵⁷⁾
3	miR-29c	miR-29c	miR-29c					Braza-Boils et al.,⁽²⁵⁾ Long et al.⁽²⁷⁾ and Joshi et al.⁽³⁹⁾
3	miR-34c	miR-34c	miR-34c					Braza-Boïls et al.,⁽²⁵⁾ Saare et al.⁽³⁴⁾ and Joshi et al.⁽³⁹⁾
3		miR-200c	miR-200c					Liang et al.,⁽³⁶⁾ Yang et al.⁽⁴³⁾ and Filigheddu et al.⁽⁴⁶⁾
3		miR-21	miR-21			miR-21		Haikalis et al.,⁽²⁶⁾ Qi et al.⁽³⁸⁾ and Azmy et al.⁽⁶²⁾
3	miR-126		miR-126			miR-126		Liu et al.,⁽²⁰⁾ Ohlsson Teague et al.⁽⁴⁵⁾ and Azmy et al.⁽⁶²⁾
3			miR-16	miR-16		miR-16		Yang et al.,⁽⁴³⁾ Suryawanshi et al.⁽⁶⁰⁾ and Azmy et al.⁽⁶²⁾
3			miR-451a		miR-451a		miR-451a	Nothnick et al.,⁽⁴⁷⁾ Cosar et al.⁽⁵¹⁾ and Marí-Alexandre et al.⁽⁶³⁾
3	miR-9		miR-9		miR-9			Wang et al.,⁽¹⁹⁾ Haikalis et al.⁽²⁶⁾ and Burney et al.⁽²⁹⁾
3			miR-106b			miR-106b	miR-106b	Yang et al.,⁽⁴³⁾ Azmy et al.⁽⁶²⁾ a^nd Marí-Alexandre et al.⁽⁶³⁾
3				miR-17	miR-17	miR-17		Wang et al.,⁽⁵³⁾ Jia et al.⁽⁶¹⁾ and Azmy et al.⁽⁶²⁾
2					miR-122		miR-122	Wang et al.⁽¹⁹⁾ and Maged et al.⁽⁵⁰⁾
2			miR-449b					Braza-Boïls et al.⁽²⁵⁾ and Zhao et al.⁽⁴²⁾
2		miR-191		miR-191	miR-191			Dong et al.⁽³⁵⁾ and Suryawanshi et al.⁽⁶⁰⁾
2	miR-202	miR-202	miR-202					Braza-Boïls et al.⁽²⁵⁾ and Filigheddu et al.⁽⁴⁶⁾
2		miR-143			miR-143			Zheng et al.⁽²²⁾ and Cosar et al.⁽⁵¹⁾
2				miR-22		miR-22		Jia et al.⁽⁶¹⁾ and Azmy et al.⁽⁶²⁾
2		miR let-7g				miR let-7g		Wright et al.⁽³¹⁾ and Azmy et al.⁽⁶²⁾
2					miR-15b	miR-15b		Wanget al.⁽⁵²⁾ and Azmy et al.⁽⁶²⁾
2			miR-125a			miR-125a		Ramón et al.⁽⁴⁴⁾ and Azmy et al.⁽⁶²⁾
2				miR-195		miR-195		Suryawanshi et al.⁽⁶⁰⁾ and Azmy et al.⁽⁶²⁾
2					miR-18a	miR-18a		Cosar et al.⁽⁵¹⁾ and Azmy et al.⁽⁶²⁾
2			miR-19b			miR-19b		Yanget al.⁽⁴³⁾ and Azmy et al.⁽⁶²⁾
2	miR-146a		miR-146a					Yang et al.⁽²¹⁾ and Yang et al.⁽⁴³⁾
2			miR-182					Zhao et al.⁽⁴²⁾ and Filigheddu et al.⁽⁴⁶⁾
2					miR-125b			Nematian et al.⁽⁴⁹⁾ and Cosar et al.⁽⁵¹⁾
2					miR-let-7b			Cho et al.⁽⁴⁸⁾ and Nematian et al.⁽⁴⁹⁾

miRNA	n	EU versus EN		EC versus EN		EC versus EU		Plasma	Serum	Blood	PF
miRNA	n	EU	EN	EC	EN	EC	EU	Plasma	Serum	Blood	PF
miR-145	6	↑ (1)	↓ (1)	↑ (1)	↓ (1)	↑ (2)	↓ (2)	↑ (1)	↑ (1) /↓ (1)
miR-200b	5			↑ (1)	↓ (1)	↓ (3)	↑ (3)	↓ (1)
miR-424	5	↓ (1)	↑ (1)			↓ (2)	↑ (2)		↑ (1)	↓ (1)
miR-199a	4	↓ (1)	↑ (1)	↓ (1)	↑ (1)			↑ (1)	↑ (2)/↓ (1)		↑ (1)
miR-141	4			↑ (1)	↓ (1)	↓ (1)	↑ (1)	↓ (1)	↓ (1)
miR-20a	4			↑ (1)	↓ (1)			↓ (1)	↓ (1)	↓ (1)
miR-200a	4			↑ (1)	↓ (1)	↓ (2)	↑ (2)	↓ (1)
miR-29c	3	↓ (1)	↑ (1)	↑ (2) /↓ (1)	↓ (2) / ↑(1)	↓ (1)	↑ (1)
miR-34c	3	↓ (1)	↑ (1)	↑ (1)	↓ (1)	↓ (1)	↑ (1)
miR-200c	3			↓ (1)	↑ (1)	↓ (2)	↑ (2)
miR-21	3			↑ (1)	↓ (1)	↓ (1)	↑ (1)			↓ (1)
miR-126	3	↓ (1)	↑ (1)			↑ (1)/↓ (1)	↓ (1)/↑ (1)			↓ (1)
miR-16	3					↑ (1)	↓ (1)	↑ (1)		↓ (1)
miR-451a	3					↑ (1)	↓ (1)		↑ (2)		↑ (1)
miR-9	3	↓ (1)	↑ (1)			↓ (1)	↑ (1)		↓ (1)
miR-106b	3					↑ (1)	↓ (1)			↓ (1)	↑ (1)
miR-17	3							↓ (1)	↓ (1)	↓ (1)
miR-122	2								↑ (2)		↑ (1)
miR-449b	2					↓ (2)	↑ (2)
miR-191	2			↑ (1)	↓ (1)			↑ (1)	↑ (1)
miR-202	2	↓ (1)	↑ (1)	↑ (1)	↓ (1)	↑ (1)	↓ (1)
miR-143	2			↑ (1)	↓ (1)				↑ (1)
miR-22	2							↓ (1)		↓ (1)
miR let-7g	2			↑ (1)	↓ (1)					↓ (1)
miR-15b	2								↓ (1)	↓ (1)
miR-125a	2					↑ (1)	↓ (1)			↓ (1)
miR-195	2							↑ (1)		↓ (1)
miR-18a	2								↑ (1)	↓ (1)
miR-19b	2					↓ (1)	↑ (1)			↓ (1)
miR-146a	2	↑ (1)	↓ (1)			↓ (1)	↑ (1)
miR-182	2					↓ (2)	↑ (2)
miR-125b	2								↑ (2)
miR-let-7b	2								↓ (2)

Instituto Israelita de Ensino e Pesquisa Albert Einstein Avenida Albert Einstein, 627/701 , 05651-901 São Paulo - SP, Tel.: (55 11) 2151 0904 - São Paulo - SP - Brazil
E-mail: revista@einstein.br

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[1] Corresponding author: Camila Hernandes Avenida Albert Einstein, 627/701 – Morumbi Zip code: 05652-900 – São Paulo, SP, Brazil Phone: (55 11) 2151-1031 E-mail: camila.hernandes@einstein.br