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Journal of Endocrinological Investigation
Erschienen in:

01.06.2019 | Original Article

Tumor suppressor miR-145-5p sensitizes prolactinoma to bromocriptine by downregulating TPT1

verfasst von: M. Jian, Q. Du, D. Zhu, Z. Mao, X. Wang, Y. Feng, Z. Xiao, H. Wang, Y. Zhu

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 6/2019

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Abstract

Purpose

Prolactinoma is the most commonly seen secretory tumor of pituitary glands, which accounts for approximately up to 40% of total pituitary adenomas. Due to its high drug resistance, dopamine agonist, such as bromocriptine, has limited effect on the treatment of patients with prolactinoma. Recent discoveries have revealed that multiple miRNAs were involved in regulating drug resistance. In this research, we explored the relationship between miR-145-5p expression as well as bromocriptine sensitivity both in vitro and in vivo.

Methods

To study the role of miR-145-5p in drug resistance of prolactinoma, the expression levels of miR-145-5p in bromocriptine-resistant prolactinoma cell line MMQ/BRC and its parental cell line MMQ cells, 24 bromocriptine-resistant as well as eight sensitive clinical samples were measured by qRT-PCR. Moreover, CCK8, flow cytometry and immunofluorescence were performed to identify the biological characteristics of MMQ/BRC and MMQ. TPT1 was predicted as a direct target gene of miR-145-5p by bioinformatic methods. In addition, qRT-PCR, western blot and immunohistochemistry were used to detect the expression level of TPT1 in clinical specimens and cell lines. Xenograft mouse model was constructed to analyze whether miR-145-5p could reverse bromocriptine resistance in prolactinoma in vivo.

Results

In our study, bromocriptine-resistant prolactinoma clinical samples and cell line had decreased miR-145-5p levels and expressed high levels of TPT1 compared with their sensitive counterparts. Bioinformatic methods and our preliminary dual luciferase reporter assay were utilized to elucidate that TPT1 was a direct target gene of miR-145-5p. Furthermore, introducing miR-145-5p mimic into MMQ cells led to a decrease of IC50 along with upregulation of TPT1; nevertheless, transfecting the corresponding inhibitor into MMQ cells resulted in an upregulation of IC50 as well as reduction of TPT1.

Conclusions

Collectively, our findings elucidated the role of miR-145-5p as an important regulator of drug resistance in prolactinoma by controlling TPT1, and implicated the potential application of miR-145-5p in cancer therapy as well.
Literatur
1.
Lake MG, Krook LS, Cruz SV (2013) Pituitary adenomas: an overview. Am Fam Physician 88(5):319–327PubMed
2.
Fernandez A, Karavitaki N, Wass JA (2010) Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 72(3):377–382CrossRef
3.
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91(12):4769–4775CrossRefPubMed
4.
Chen CH, Xiao WW, Jiang XB, Wang JW, Mao ZG, Lei N et al (2013) A novel marine drug, SZ-685C, induces apoptosis of MMQ pituitary tumor cells by downregulating miR-200c. Curr Med Chem 20(16):2145–2154CrossRefPubMed
5.
Dos SSC, Barbosa FR, Lima GA, Warszawski L, Fontes R, Domingues RC et al (2011) BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring) 19(4):800–805CrossRef
6.
Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA et al (2011) Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(2):273–288CrossRefPubMed
7.
Jiang XB, Hu B, He DS, Mao ZG, Wang X, Song BB et al (2015) Expression profiling of O(6) methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases. BMC Cancer 15:644CrossRefPubMedPubMedCentral
8.
Hamilton DK, Vance ML, Boulos PT, Laws ER (2005) Surgical outcomes in hyporesponsive prolactinomas: analysis of patients with resistance or intolerance to dopamine agonists. Pituitary 8(1):53–60CrossRefPubMed
9.
Alberiche RM, Boronat CM, Ojeda PA, Rodriguez PC, Gracia NM, Marrero AD et al (2010) Acquired resistance to cabergoline: progression from initially responsive micro to macroprolactinoma. Pituitary 13(4):380–382CrossRef
10.
Passos VQ, Fortes MA, Giannella-Neto D, Bronstein MD (2009) Genes differentially expressed in prolactinomas responsive and resistant to dopamine agonists. Neuroendocrinology 89(2):163–170CrossRefPubMed
11.
Cuny T, Mohamed A, Graillon T, Roche C, Defilles C, Germanetti AL et al (2012) Somatostatin receptor sst2 gene transfer in human prolactinomas in vitro: impact on sensitivity to dopamine, somatostatin and dopastatin, in the control of prolactin secretion. Mol Cell Endocrinol 355(1):106–113CrossRefPubMed
12.
Caccavelli L, Feron F, Morange I, Rouer E, Benarous R, Dewailly D et al (1994) Decreased expression of the two D2 dopamine receptor isoforms in bromocriptine-resistant prolactinomas. Neuroendocrinology 60(3):314–322CrossRefPubMed
13.
Li Z, Liu Q, Li C, Zong X, Bai J, Wu Y et al (2015) The role of TGF-beta/Smad signaling in dopamine agonist-resistant prolactinomas. Mol Cell Endocrinol 402:64–71CrossRefPubMed
14.
Paez-Pereda M, Kuchenbauer F, Arzt E, Stalla GK (2005) Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix. Braz J Med Biol Res 38(10):1487–1494CrossRefPubMed
15.
Cristina C, Diaz-Torga G, Baldi A, Gongora A, Rubinstein M, Low MJ et al (2005) Increased pituitary vascular endothelial growth factor-a in dopaminergic D2 receptor knockout female mice. Endocrinology 146(7):2952–2962CrossRefPubMed
16.
Cristina C, Diaz-Torga G, Gongora A, Guida MC, Perez-Millan MI, Baldi A et al (2007) Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice. Am J Physiol Endocrinol Metab 293(5):E1341–E1351CrossRefPubMed
17.
Chen CZ (2005) MicroRNAs as oncogenes and tumor suppressors. N Engl J Med 353(17):1768–1771CrossRefPubMed
18.
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297CrossRefPubMed
19.
Chen GQ, Zhao ZW, Zhou HY, Liu YJ, Yang HJ (2010) Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin. Med Oncol 27(2):406–415CrossRefPubMed
20.
Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer 127(8):1785–1794CrossRefPubMed
21.
Zhang W, Zhou J, Zhu X, Yuan H (2017) MiR-126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer. Gene 627:420–427CrossRefPubMed
22.
Yang D, Zhan M, Chen T, Chen W, Zhang Y, Xu S et al (2017) miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer. Sci Rep 7:43109CrossRefPubMedPubMedCentral
23.
Pan YZ, Zhou A, Hu Z, Yu AM (2013) Small nucleolar RNA-derived microRNA hsa-miR-1291 modulates cellular drug disposition through direct targeting of ABC transporter ABCC1. Drug Metab Dispos 41(10):1744–1751CrossRefPubMedPubMedCentral
24.
Song B, Wang Y, Xi Y, Kudo K, Bruheim S, Botchkina GI et al (2009) Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene 28(46):4065–4074CrossRefPubMedPubMedCentral
25.
Li E, Zhang J, Yuan T, Ma B (2014) MiR-145 inhibits osteosarcoma cells proliferation and invasion by targeting ROCK1. Tumour Biol 35(8):7645–7650CrossRefPubMed
26.
Kou B, Gao Y, Du C, Shi Q, Xu S, Wang CQ et al (2014) miR-145 inhibits invasion of bladder cancer cells by targeting PAK1. Urol Oncol 32(6):846–854CrossRefPubMed
27.
Lu R, Ji Z, Li X, Zhai Q, Zhao C, Jiang Z et al (2014) miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin Oncol 140(3):387–397CrossRefPubMed
28.
Wang H, Hang C, Ou XL, Nie JS, Ding YT, Xue SG et al (2016) MiR-145 functions as a tumor suppressor via regulating angiopoietin-2 in pancreatic cancer cells. Cancer Cell Int 16(1):65CrossRefPubMedPubMedCentral
29.
Derouet MF, Liu G, Darling GE (2014) MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance. PLoS One 9(12):e115589CrossRefPubMedPubMedCentral
30.
Zhang J, Wang L, Li B, Huo M, Mu M, Liu J et al (2014) miR-145 downregulates the expression of cyclin-dependent kinase 6 in human cervical carcinoma cells. Exp Ther Med 8(2):591–594CrossRefPubMedPubMedCentral
31.
Liu RL, Dong Y, Deng YZ, Wang WJ, Li WD (2015) Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer. Tumour Biol 36(7):5011–5019CrossRefPubMed
32.
Zhu X, Li Y, Xie C, Yin X, Liu Y, Cao Y et al (2014) miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6. Int J Cancer 135(6):1286–1296CrossRefPubMed
33.
Zhan M, Zhao X, Wang H, Chen W, Xu S, Wang W et al (2016) miR-145 sensitizes gallbladder cancer to cisplatin by regulating multidrug resistance associated protein 1. Tumour Biol 37(8):10553–10562CrossRefPubMed
34.
Gao M, Miao L, Liu M, Li C, Yu C, Yan H et al (2016) miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1. Oncotarget 7(37):59714–59726PubMedPubMedCentral
35.
Bommer UA, Thiele BJ (2004) The translationally controlled tumour protein (TCTP). Int J Biochem Cell Biol 36(3):379–385CrossRefPubMed
36.
Chen W, Wang H, Tao S, Zheng Y, Wu W, Lian F et al (2013) Tumor protein translationally controlled 1 is a p53 target gene that promotes cell survival. Cell Cycle 12(14):2321–2328CrossRefPubMedPubMedCentral
37.
Li Y, Sun H, Zhang C, Liu J, Zhang H, Fan F et al (2017) Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics. Oncogene 36(50):6839–6849CrossRefPubMedPubMedCentral
38.
Sala E, Bellaviti BP, Malchiodi E, Verrua E, Carosi G, Profka E et al (2016) Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas. J Endocrinol Invest 39(12):1377–1382CrossRefPubMed
39.
Colao A, Di Sarno A, Guerra E, De Leo M, Mentone A, Lombardi G (2006) Drug insight: cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women. Nat Clin Pract Endocrinol Metab 2(4):200–210CrossRefPubMed
40.
Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R et al (2001) Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab 86(11):5256–5261CrossRefPubMed
41.
Pellicciotta I, Yang CP, Venditti CA, Goldberg GL, Shahabi S (2013) Response to microtubule-interacting agents in primary epithelial ovarian cancer cells. Cancer Cell Int 13(1):33CrossRefPubMedPubMedCentral
42.
Gachet Y, Tournier S, Lee M, Lazaris-Karatzas A, Poulton T, Bommer UA (1999) The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle. J Cell Sci 112(Pt 8):1257–1271PubMed
43.
Boia-Ferreira M, Basilio AB, Hamasaki AE, Matsubara FH, Appel MH, Da CC et al (2017) TCTP as a therapeutic target in melanoma treatment. Br J Cancer 117(5):656–665CrossRefPubMedPubMedCentral
44.
Bommer UA (2017) The translational controlled tumour protein TCTP: biological functions and regulation. Results Probl Cell Differ 64:69–126CrossRefPubMed
45.
Diraison F, Hayward K, Sanders KL, Brozzi F, Lajus S, Hancock J et al (2011) Translationally controlled tumour protein (TCTP) is a novel glucose-regulated protein that is important for survival of pancreatic beta cells. Diabetologia 54(2):368–379CrossRefPubMed
46.
Sinha P, Kohl S, Fischer J, Hutter G, Kern M, Kottgen E et al (2000) Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis. Electrophoresis 21(14):3048–3057CrossRefPubMed
47.
Bommer UA, Vine KL, Puri P, Engel M, Belfiore L, Fildes K et al (2017) Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin. Cell Commun Signal 15(1):9CrossRefPubMedPubMedCentral
Metadaten
Titel
Tumor suppressor miR-145-5p sensitizes prolactinoma to bromocriptine by downregulating TPT1
verfasst von
M. Jian
Q. Du
D. Zhu
Z. Mao
X. Wang
Y. Feng
Z. Xiao
H. Wang
Y. Zhu
Publikationsdatum
01.06.2019
Verlag
Springer International Publishing
Erschienen in
Journal of Endocrinological Investigation / Ausgabe 6/2019
Elektronische ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-018-0963-4

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