Evidence map›Paper›PMID 26676464›Full record

ArticleInternational journal of oncology2016

PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer.

Li-Xu Yan, Yan-Hui Liu, Jian-Wen Xiang, Qi-Nian Wu, Lei-Bo Xu, Xin-Lan Luo, Xiao-Lan Zhu, Chao Liu, Fang-Ping Xu, Dong-Lan Luo and 4 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.

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  8. Cancer-AssociatedInternational journal of medical sciences · 2025
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Li-Xu YanDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Yan-Hui LiuDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Jian-Wen XiangGuangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Qi-Nian WuThe First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
Lei-Bo XuSun Yat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guangdong, P.R. China.
Xin-Lan LuoDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Xiao-Lan ZhuDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Chao LiuDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Fang-Ping XuDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Dong-Lan LuoDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Ping MeiDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Jie XuDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Ke-Ping ZhangDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Jie ChenDepartment of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, P.R. China.
Guangdong General Hospital · CNGuangdong Academy of Medical Sciences · CNGuangdong Provincial Hospital of Traditional Chinese Medicine · CNGuangzhou Medical University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), and detected PIK3R1 coding protein (p85α) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85α overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR‑21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85α, accompanied by decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85α downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85α downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS, which may require more aggressive treatment.

Indexed as

Breast NeoplasmsCell Line, TumorCell MovementCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDisease-Free SurvivalDown-RegulationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMicroRNAsNeoplasm InvasivenessPhosphatidylinositol 3-KinasesPrognosisClass Ia Phosphatidylinositol 3-KinaseMicroRNAsMIRN21 microRNA, humanPhosphatidylinositol 3-KinasesPIK3R1 protein, humanProto-Oncogene Proteins c-akt

Identifiers

PMID26676464
PMCPMC4725461
OpenAlexW2190259787

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.