MicroRNA-452 promotes stem-like cells of hepatocellular carcinoma by inhibiting Sox7 involving Wnt/β-catenin signaling pathway
Why this work is in the frame
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Bibliographic record
Abstract
// Zhiyun Zheng 1 , Jimin Liu 1, 2 , Zhe Yang 1 , Limin Wu 1 , Haiyang Xie 1 , Chaozhe Jiang 1 , Binyi Lin 1 , Tianchi Chen 1 , Chunyang Xing 1 , Zhikun Liu 1 , Penghong Song 1 , Shengyong Yin 1 , Shusen Zheng 1, 3 , Lin Zhou 1 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China 2 Department of Pathology and Molecular Medicine, Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada 3 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China Correspondence to: Shusen Zheng, email: shusenzheng@zju.edu.cn Lin Zhou, email: linzhou19@163.com Keywords: miRNAs, liver cancer, CSCs, β-catenin, ATRA Received: November 13, 2015 Accepted: February 15, 2016 Published: April 05, 2016 ABSTRACT The decrease of microRNA-452 (miR-452) in gliomas promoted stem-like features and tumorigenesis. However, the role of miR-452, especially in regulating cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) remains ambiguous. We enriched stem-like HCC cells by serial passages of hepatospheres with chemotherapeutic agents. Stem-like characteristics including the capabilities of chemo-resistance, stemness-related gene expression profiling, self-renewal, tumorigenicity and metastasis formation were detected. MiR-452 was markedly increased in the chemo-resistant hepatospheres and human HCC tissues. and the overexpression of miR-452 in HCC patients predicted poor overall survival. MiR-452 significantly promoted stem-like characteristics in vitro and in vivo . Further, Sox7 was identified as the direct target of miR-452, which could physically bind with β-catenin and TCF4 in the nucleus and then inhibit the activity of Wnt/β-catenin signaling pathway. Finally, the combined chemotherapy of doxorubicin and all-trans retinoic acid (ATRA) showed dramatically efficiency in suppressing HCC metastasis. These data suggested that miR-452 promoted stem-like traits of HCC, which might be a potential therapeutic target for HCC. The combination of doxorubicin and ATRA might be a promising therapy in HCC management.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it