MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer

Abstract

BackgroundRadioresistance is a challenge in the treatment of patients with colorectal cancer (CRC). Individuals display different therapeutic responses to preoperative radiotherapy, and the need of targeted therapies is urgent. MicroRNAs (miRNAs) are involved in essential biological activities, including chemoresistance and radioresistance. Several research studies have indicated that miRNA played an important role in sensitizing cells to ionizing radiation (IR). MiR-106b, a member of the miR-106b-25 cluster, is frequently dysregulated in many human cancers, including CRC. However, the function of miR-106b in radioresistance is currently poorly understood.MethodsA series of in vitro and in vivo studies were performed to investigate the roles of miR-106b on cell radioresistance in CRC.ResultsWe found overexpression of miR-106b could induce resistance to IR in vitro and in vivo in SW620 cells. Correspondingly, knocking down miR-106b in SW480 yielded the opposite effect. In addition, overexpression of miR-106b could enhance the tumour-initiating cell capacity without or with IR condition, such as the colony sphere formation capacity and the upregulation of stemness-related genes (CD133, Sox2). We further identified PTEN and p21 as novel direct targets of miR-106b by using target prediction algorithms and a luciferase assay. Overexpression of miR-106b reduced the expression of PTEN and p21 and increased the expression of p-AKT, which is a downstream of PTEN. Restoring the expression of PTEN or p21 in stably miR-106b-overexpressed cells could rescue the effect of miR-106b on cell radioresistance. Together, the acquisition of tumour-initiating cell capacity endowed CRC cells with the potential of resistance to irradiation.ConclusionsThese observations illustrated that miR-106b could induce cell radioresistance by directly targeting PTEN and p21, this process was accompanied by tumour-initiating cell capacity enhancement, which is universally confirmed to be associated with radioresistance. Our data suggested that miR-106b at least partly induces cell radioresistance in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0592-z) contains supplementary material, which is available to authorized users.

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1

“…36 Moreover, miR-106b induced cell radioresistance, and miR-520g conferred drug resistance in colorectal cancer both by regulating p21 expression. 39,40 And, miR-224 promoted the chemoresistance of A549 cells to cisplatin by targeting p21 as well. 41 Our data that miR-33b-3p attenuated the cisplatin sensitivity of A549 cells by direct diminishing the p21 expression, was in consistent with above published literatures.…”

miR-106b promotes cell invasion and metastasis via PTEN mediated EMT in ESCC

“…Several genes have been verified to be the targets of miR-106b, including transforming growth factor-β type II receptor, cyclin dependent kinase inhibitor 1A, DLC-1 Rho GTPase activating protein, signal transducer and activator of transcription 3 and mitogen-activated protein kinase 14 (7,(10)(11)(12). Phosphatase and tensin homolog (PTEN), a key negative regulator of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, is also a direct target of miR-106b (13). One previous study had reported that PTEN served as a tumor-suppressing gene in cancer invasion and metastasis (14).…”

Betulinic acid increases radiosensitization of oral squamous cell carcinoma through inducing Sp1 sumoylation and PTEN expression

“…Activation of PTEN by COX-2 inhibitors could induce cancer cell radiosensitivity (34). miRNA29a, miRNA21, miRNA16b could regulate radiosensitivity through targeting PTEN (35)(36)(37). PTEN/PI3K/AKT pathways were demonstrated mediating radiosensitivity (35).…”

“…miRNA29a, miRNA21, miRNA16b could regulate radiosensitivity through targeting PTEN (35)(36)(37). PTEN/PI3K/AKT pathways were demonstrated mediating radiosensitivity (35). PTEN/Akt/HIF-1α feedback loop modulates miRNA210-induced radiosensitivity (37).…”