407006

MIR221

microRNA 221;MIR221;microRNA 221

hsa-mir-221

Xp11.3

ncRNA

HER2-overexpressing breast cancers are characterized by frequent distant metastasis and often develop resistance after short-term effective treatment with the monoclonal antibody drug, trastuzumab. Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was identified as a miR-221 target; overexpression of PTEN abrogated the aforementioned miR-221-induced malignant phenotypes of the cells. These findings indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2-positive breast cancers by targeting PTEN, suggesting its role as a potential biomarker for progression and poor prognosis, and as a novel target for trastuzumab-combined treatment of breast cancers.

OBJECTIVE: MicroRNA-221 (miR-221), which is located on chromosome X, is an oncogenic microRNA that is involved in several human malignancies. This study aimed to characterize the role of miR-221 in the initiation and malignant progression of gastric cancer. METHODS: The level of miR-221 expression in 92 pairs of primary gastric tumour tissue and adjacent nontumour tissue was quantified by real-time reverse transcription-polymerase chain reaction. The relationship between the miR-221 level and clinicopathological features was explored. RESULTS: MiR-221 was up-regulated in 88% (81/92) of gastric cancer tissue samples compared with their paired adjacent nontumour tissue samples. High expression of miR-221 showed a significant correlation with advanced tumour-node-metastasis stage, local invasion and lymphatic metastasis. Univariate and multivariate Cox proportional hazard regression analyses revealed that miR-221 overexpression was an unfavourable prognostic factor for overall survival in patients with gastric cancer. CONCLUSIONS: These findings suggest that miR-221 is a novel prognostic indicator in gastric cancer and may be a potential target for diagnosis and gene therapy.

Aberrant expression of specific microRNAs in hepatocellular carcinomas has recently been reported. We examined expression patterns of 4 microRNAs (microRNA-221, microRNA-222, microRNA-21, and microRNA-155) to evaluate their potential as relevant biomarkers by quantitative real-time reverse transcriptase-polymerase chain reaction using formalin-fixed, paraffin-embedded tissues of 115 surgically resected hepatocellular carcinoma and paired nonneoplastic liver cases as well as 21 normal liver samples from cancer-free individuals. MicroRNA-221, microRNA-222, and microRNA-21 were differentially overexpressed in hepatocellular carcinoma compared with nonneoplastic and normal livers (P < .001). The mean fold changes in microRNA-221, microRNA-222, and microRNA-21(hepatocellular carcinoma to matched nonneoplastic liver) were 4.00, 4.44, and, 3.67, respectively. In addition, nonneoplastic liver tissues displayed higher levels of microRNA-221, microRNA-222, microRNA-21, and microRNA-155 than normal livers (P < .001, respectively). However, the overexpression of the 4 microRNAs showed no consistent relevance to the known prognostic clinicopathologic parameters. High expression of microRNA-221 in hepatocellular carcinomas was significantly related to shorter time to local recurrence (P < .001) and determined as an independent predictor for local recurrence (P = .001). The fold changes in microRNA-221 (hepatocellular carcinoma to matched nonneoplastic liver) less than 1 were more commonly detected in cases of distant metastases than those of disease-free and local recurrence (P = .009). The fold changes less than 1 were related to reduced metastasis-free survival (P = .006) and thus can be used as an independent predictor of distant metastasis after surgical resection (P = .027). Based on these results, we propose the possible role of microRNA-221, microRNA-222, microRNA-21, and microRNA-155 dysregulation in hepatocarcinogenesis and the potential of microRNA-221 dysregulation for predicting local recurrence and distant metastasis after curative surgery.