Abstract P4-07-19: MicroRNA miR-24 enhances tumor angiogenesis and metastasis in breast cancer
Bibliographic record
Abstract
Abstract MicroRNAs (miRNA) are non-coding single-stranded RNA molecules, which are produced from endogenous transcripts of short stem-loop structures. Through binding to the 3’-untranslated region (3’UTR) of different target messenger RNAs (mRNAs), microRNAs can repress the translation of the target mRNAs. Recent studies have shown that miR-24 can inhibit apoptosis of cancer cells and cardiomyocytes, and can accelerate cell proliferation. Up-regulation of miR-24 has been observed in oral carcinoma and is one of the most abundant miRNAs in cervical cancer. However, the role of miR-24 in breast cancer cell angiogenesis and metastasis is not clear. We analyzed microRNA miR-24 levels in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in breast benign tissues. We generated constructs expressing miR-24 and studied its functions using both in vitro and in vivo techniques. We found that the ectopic expression of miR-24 promoted breast cancer angiogenesis and metastasis. Cell migration assays indicated that expression of miR-24 promoted migration of MT-1 cells and 4T1 cells. We examined proliferation of MT-1 cells and 4T1 cells transfected with miR-24 or the control vector. The experiments showed that the miR-24 transfected cells had high rates of proliferation than the vector-transfected cells. In vivo experiments indicated that the expression of miR-24 enhanced tumor growth, metastasis to lung tissues, and decreased overall mouse survival. Tumor sections were also probed with anti-CD34 antibody to examine angiogenesis. We found that miR-24 expression increased tumor-associated vascularization. We further performed tumor metastatic assays. DNA was isolated from lung tissues and subjected to PCR to indicate metastasis of the cancer cells. Typical metastatic lesions in the lungs are shown. In the miR-24 expressing cells and tumors, expression of the phosphatases PTPN9 and PTPRF were repressed. We confirmed that miR-24 could directly target both PTPN9 and PTPRF. Consistent with this, we found that the levels of PTPN9 and PTPRF were lower in the patients with metastatic breast carcinoma. Ectopic expression of PTPN9 and PTPRF decreased cell migration, and tumor metastasis. Our study demonstrates that miR-24 is highly expressed in human breast carcinoma. This finding suggests a role of miR-24 in breast cancer development/progression. Our results suggest that miR-24 plays a key role in breast cancer angiogenesis and metastasis. miR-24 could potentially be a target for cancer intervention. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-19.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".