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Published on: May 20, 2015
Identification of Novel piR-2158 Isoforms and Their Distinct Antitumor Effects on Triple-Negative Breast Cancer
Zhongrui Wang1,2, Yu Liu1,3, Lu Qian1,4
1Medical Innovation Center and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China.
Background:
The diversity of RNA isoforms plays a critical role in regulating the development and progression of human cancers. Our previous work has demonstrated that piR-2158 exerts antitumor activity in breast cancer by repressing IL11-STAT3 signaling.
Methods:
The isoforms of piR-2158 were analyzed using Sanger sequencing, quantitative real-time PCR (qRT-PCR), and Gene Expression Omnibus (GEO) dataset. Cell proliferation capacity was assessed using Cell Counting Kit-8 (CCK-8) assays and Ki67 immunofluorescence staining. Cell migration was evaluated using wound healing assays. Cancer cell stemness was analyzed using mammosphere formation assay, stemness marker detection, and ALDH activity assay.
Results:
We identified two types of piR-2158 isoforms in mammary tissues: a 31 nt long isopiR (designated as iso-piR-2158-L) and a 28 nt short isopiR (designated as iso-piR-2158-S). Predominant expression of iso-piR-2158-L was observed in normal mammary epithelial cells and adjacent non-tumor breast tissues, whereas it was significantly downregulated in TNBC cell lines and primary tumor tissues. We experimentally demonstrated that iso-piR-2158-L and iso-piR-2158-S exert distinct effects on TNBC cell proliferation, migration, and stemness, with iso-piR-2158-L showing significantly stronger antitumor effects than iso-piR-2158-S. Subsequent mechanistic studies revealed that iso-piR-2158-L suppresses IL11 expression more effectively, compared to iso-piR-2158-S.
Conclusions:
Our findings reveal a piRNA isoform-based regulatory pathway that may be involved in regulating pathological transformation, tumor initiation, and progression in TNBC.
Insights
Two piR-2158 RNA isoforms were identified in breast cancer, with the longer isoform (iso-piR-2158-L) showing stronger tumor-suppressing activity by inhibiting IL11 expression.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- RNA isoforms are crucial regulators in human cancer development and progression.
- Previous studies indicated piR-2158 has antitumor effects in breast cancer via IL11-STAT3 signaling inhibition.
Purpose of the Study:
- To investigate the distinct roles and mechanisms of piR-2158 isoforms in triple-negative breast cancer (TNBC).
- To identify potential therapeutic targets based on piRNA isoform activity.
Main Methods:
- Analysis of piR-2158 isoforms using Sanger sequencing, qRT-PCR, and GEO datasets.
- Assessment of cell proliferation, migration, and stemness using CCK-8 assays, Ki67 staining, wound healing assays, mammosphere formation, and ALDH activity assays.
Main Results:
- Two piR-2158 isoforms, iso-piR-2158-L (31 nt) and iso-piR-2158-S (28 nt), were identified.
- iso-piR-2158-L was downregulated in TNBC and exhibited stronger inhibition of proliferation, migration, and stemness compared to iso-piR-2158-S.
- iso-piR-2158-L demonstrated more effective suppression of IL11 expression than iso-piR-2158-S.
Conclusions:
- A piRNA isoform-specific regulatory pathway is implicated in TNBC pathological transformation, initiation, and progression.
- Findings suggest differential functions of piRNA isoforms in cancer, offering potential for targeted therapies.
