442893

MIR151A

microRNA 151a;MIR151A;microRNA 151a

microRNA 151

-

ncRNA

BACKGROUND: MicroRNAs (miRNAs) may function as suppressors or promoters of tumor metastasis according to their messenger RNA targets. Previous studies have suggested that miR-9 and miR-151-5p are associated with metastasis in breast cancer and hepatocellular carcinoma, respectively. We aimed to further establish the potential roles of miR-9 and miR-151-5p in tumor invasion and metastasis and investigate their use as biomarkers. METHODS: We used quantitative real-time PCR (qRT-PCR) to measure differences in miR-9 and miR-151-5p expression between primary breast tumors and their lymph-node metastases in 194 paired tumor samples from 97 patients. We also correlated expression levels with histologic data to investigate their utility as biomarkers. RESULTS: There were no significant differences in miR-9 expression between the primary tumors and lymph nodes; however, miR-151-5p expression was significantly lower in the lymph-node metastases than in their corresponding tumors (p < 0.05). miR-9 levels were elevated in primary breast tumors from patients diagnosed with higher-grade tumors (p < 0.05); however, no differences were observed in miR-151-5p levels between different grades of tumor. Interestingly, miR-9 levels were elevated in invasive lobular carcinomas (ILC) compared with invasive ductal carcinomas (IDC; p < 0.01). CONCLUSIONS: In aggregate, these data suggest that miR-151-5p upregulation may suppress metastasis in primary breast tumors. Both miRNAs may serve as useful biomarkers in future clinical trials in breast cancer.

Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma (HCC), but little is known about the functional non-coding sequences, particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic metastasis of HCC. We further show that miR-151, which is often expressed together with its host gene FAK, encoding focal adhesion kinase, significantly increases HCC cell migration and invasion in vitro and in vivo, mainly through miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading. Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus for tumour invasion and metastasis of HCC.

BACKGROUND: Radical prostatectomy (RP) is not curative if patients have undetected metastatic prostate cancer. Markers that indicate the presence of metastatic disease would identify men who may benefit from systemic adjuvant therapy. Our approach was to analyze the primary tumors of men with metastatic disease versus organ-confined disease to identify molecular changes that distinguish between these groups. METHODS: Patients were identified based on long-term follow-up of serum prostate specific antigen (PSA) levels following RP. We compared the tumors of African American (AA) men with undetectable serum PSA for >9 year after RP (good outcome) versus those of AA men with a rising PSA and recurrence after radiation or androgen ablation or both (poor outcome). We used real-time quantitative PCR to assay gene copy number alterations in tumor DNA relative to patient-matched non-tumor DNA isolated from paraffin-embedded tissue. We assayed several genes located in the specific regions of chromosome 8p and 8q that frequently undergo loss and/or gain, respectively, in prostate cancer, and the androgen receptor gene at Xq12. RESULTS: Gain of the MIR151 gene at 8q24.3 (in 33% of poor outcome vs. 6% of good outcome tumors) and/or loss of the NKX3-1 gene at 8p21.2 (in 39% of poor outcome vs. 11% of good outcome tumors) affected 67% of poor outcome tumors, compared to only 17% of good outcome tumors. CONCLUSIONS: copy number gain of the MIR151 gene and/or loss of the NKX3-1 gene in the primary tumor may indicate the presence of metastatic disease.