Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene

被引：8

作者：

Cenariu, Diana ^{[1
]}

Zimta, Alina-Andreea ^{[1
]}

Munteanu, Raluca ^{[1
]}

Onaciu, Anca ^{[1
]}

Moldovan, Cristian Silviu ^{[1
]}

Jurj, Ancuta ^{[2
]}

Raduly, Lajos ^{[2
]}

Moldovan, Alin ^{[1
]}

Florea, Adrian ^{[3
]}

Budisan, Liviuta ^{[2
]}

Pop, Laura Ancuta ^{[2
]}

Magdo, Lorand ^{[4
]}

Albu, Mihai Tudor ^{[4
]}

Tonea, Rares Bogdan ^{[4
]}

Muresan, Mihai-Stefan ^{[5
,6
,7
]}

Ionescu, Calin ^{[5
,7
]}

Petrut, Bogdan ^{[8
,9
]}

Buiga, Rares ^{[10
,11
]}

Irimie, Alexandru ^{[12
,13
]}

Gulei, Diana ^{[1
]}

Berindan-Neagoe, Ioana ^{[2
,14
]}

机构：

[1] Iuliu Hatieganu Univ Med & Pharm, MEDFUTURE Res Ctr Adv Med, Marinescu 23 St Louis Pasteur 4-6 St, Cluj Napoca 400337, Romania

[2] Iuliu Hatieganu Univ Med & Pharm, Res Ctr Funct Genom Biomed & Translat Med, 23 Marinescu St, Cluj Napoca 400337, Romania

[3] Iuliu Ha Ieganu Univ Med & Pharm, Fac Med, Dept Cell & Mol Biol, Cluj Napoca 400349, Romania

[4] Iuliu Hatieganu Univ Med & Pharm, Fac Med, 8 Victor Babes St, Cluj Napoca 400012, Romania

[5] Municipal Hosp, Surg Dept 5, 11 Tabacarilor St, Cluj Napoca 400139, Romania

[6] Prof Dr Ion Chiricuta Oncol Inst, Surg & Gynecol Oncol Dept, Republicii 34-36 St, Cluj Napoca 400015, Romania

[7] Iuliu Hatieganu Univ Med & Pharm, Dept Surg 5, 8 Victor Babes St, Cluj Napoca 400012, Romania

[8] Prof Dr Ion Chiricuta Oncol Inst, Dept Urol, Republicii 34-36 St, Cluj Napoca 400015, Romania

[9] Iuliu Hatieganu Univ Med & Pharm, Dept Urol, 8 Victor Babes St, Cluj Napoca 400012, Romania

[10] Prof Dr Ion Chiricuta Oncol Inst, Dept Pathol, Republicii 34-36 St, Cluj Napoca 400015, Romania

[11] Iuliu Hatieganu Univ Med & Pharm, Dept Pathol, 8 Victor Babes St, Cluj Napoca 400012, Romania

[12] Iuliu Hatieganu Univ Med & Pharm, Dept Surg Oncol & Gynaecol Oncol 11, 8 Victor Babes St, Cluj Napoca 400012, Romania

[13] Oncol Inst Prof Dr Ion Chiricuta, Dept Surg, 34-36 Republicii St, Cluj Napoca 400015, Romania

[14] Prof Dr Ion Chiricuta Oncol Inst, Dept Funct Genom & Expt Pathol, 34-36 Republicii St, Cluj Napoca 400015, Romania

来源：

PHARMACEUTICS | 2021年 / 13卷 / 05期

关键词：

colon cancer; colorectal cancer; miR-125b; therapy; TP53; mutation; PROGNOSTIC-FACTOR; EXPRESSION; MIR-125B; BCL-2; P53;

D O I：

10.3390/pharmaceutics13050664

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the TP53 gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically TP53 in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the TP53 mutation status of colon cancer cell lines. In TP53 mutated models, miR-125b-5p overexpression slows cancer cells' malignant behavior by inhibiting the invasion/migration and colony formation capacity via direct downregulation of mutated TP53. In TP53 wild type cells, the exogenous modulation of miR-125b-5p did not significantly affect the molecular and phenotypic profile. In conclusion, our data show that miR-125b-5p has an anti-cancer effect only in TP53 mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies.

引用

页数：20

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