MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer

Abstract

Abstract. Accumulating evidence has demonstrated that aberrant miRNAs contribute to cervical cancer (CC) development and progression. However, the roles of various miRNAs in CC remain to be determined. In the present study, we confirmed that a decreased miR-1297 expression was present in CC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-1297 expression was significantly correlated with poor prognostic features including lymph node metastasis and lymphovascular space invasion. Moreover, we confirmed that miR-1297 was a novel independent prognostic marker for predicting the 5-year survival of CC patients. The ectopic overexpression of miR-1297 inhibited cell migration, invasion and EMT progression, while downregulated miR-1297 reversed these effects. In addition, miR-1297 regulated AEG-1 by directly binding to its 3'-UTR. In clinical samples of CC, miR-1297 was inversely correlated with AEG-1, which was upregulated in CC. Alteration of AEG-1 expression at least partially abolished the migration, invasion and EMT progression effects of miR-1297 on CC cells. In conclusion, our results indicated that miR-1297 functioned as a tumor suppressor gene in regulating the EMT and metastasis of CC via targeting of AEG-1, and may represent a novel potential therapeutic target and prognostic marker for CC.

The role of miRNAs in the invasion and metastasis of cervical cancer

“…AEG-1, also known as metadherin (MTDH), and lysine-rich CEACAM1 co-isolate protein (LYRIC) greatly participate in carcinogenesis and tumor progression in several malignancies. Fortunately, it was also discovered by Wang et al [129] that alteration of AEG-1 eliminates the suppressive effects of miR-1297 on the metastasis of CC and EMT. The down-regulation of miR-145 might generate EMT and the metastasis of CC in conjunction with up-regulated expression of SMAD-interacting protein 1 (SIP1, also known as ZEB2) [130].…”

“…With regard to the diagnosis and treatment of metastatic CC, researchers have studied cervical tissues and found a relationship between miRNAs and the diagnosis and treatment of metastatic CC. It was of interest to find that decreased miR-99a/b [90], miR-125a [139], miR-138 [75], miR-140-5p [85], miR-144 [66], miR-195 [127], miR-205 [88], miR-214 [91], miR-218 [96,133,148,167], miR-329-3p [57], miR-337 [68], miR-362 [94], miR-374c-5p [143], miR-375 [67], miR-377 [126], miR-379 [104], miR-485 [105], miR-486-3p [62], miR-638 [123], and miR-1297 [129] expression strongly correlate with tumor size, TNM stage, tissue pathology grade, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, or distant metastasis in patients with CC. In addition, overexpressed miR-20a [31], miR-21 [168], miR-92a [118], miR-145 [79], miR-195 [166], miR-199b-5p [169], and miR-501 [51] closely correlate with histological grade, tumor diameter, overall survival (OS), progression-free survival (PFS), late FIGO stages, lymph node metastasis, or preoperative metastasis.…”

Long Non-Coding RNA ZEB1-Antisense 1 Affects Cell Migration and Invasion of Cervical Cancer by Regulating Epithelial-Mesenchymal Transition via the p38MAPK Signaling Pathway

“…The metastasis of cervical cancer is a process concerning multi-factor, multi-step, and continuous cascade reactions [4]. In the study of cervical cancer metastasis, epithelial-mesenchymal transition (EMT), as the key link in the metastatic cascade, has attracted more and more attention from scholars at home and abroad [5,6].…”

<p>miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2</p>

“… 17 Wang et al found that miR-1297 inhibited metastasis by targeting AEG-1 in cervical cancer. 18 Wang et al reported that serum miR-1297 is a promising diagnostic biomarker in esophageal squamous cell carcinoma. 19 Therefore, miR-1297 is an effective target for the treatment of tumors.…”