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Published on: July 6, 2019
miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis
Yang Xia1, Ke Wei1, Feng-Ming Yang2
1Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Abstract:
Non-small cell lung cancer (NSCLC) is one of the most common aggressive malignancies. miRNAs have been identified as important biomarkers and regulators of NSCLC. However, the functional contributions of miR-1260b to NSCLC cell proliferation and apoptosis have not been studied. In this study, miR-1260b was upregulated in NSCLC plasma, tissues, and cell lines, and its high expression was correlated with tumor size and progression. Functionally, miR-1260b overexpression promoted cell proliferation and cell cycle, conversely inhibited cell apoptosis and senescence. Mechanically, miR-1260b negatively regulated SOCS6 by directly binding to its 3'-UTR. Furthermore, miR-1260b-mediated suppression of SOCS6 activated KIT signaling. Moreover, YY1 was an upstream regulator of miR-1260b. This study is the first to illustrate that miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate NSCLC cell proliferation and apoptosis, and is a potential biomarker and therapeutic target for NSCLC. In sum, our work provides new insights into the molecular mechanisms of NSCLC involved in cell proliferation and apoptosis.
Insights
MicroRNA-1260b (miR-1260b) promotes non-small cell lung cancer (NSCLC) growth and survival by targeting SOCS6 and activating KIT signaling. This study identifies miR-1260b as a potential biomarker and therapeutic target for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-small cell lung cancer (NSCLC) is a prevalent and aggressive malignancy.
- MicroRNAs (miRNAs) are recognized as crucial regulators and biomarkers in NSCLC.
- The specific role of miR-1260b in NSCLC proliferation and apoptosis remained uninvestigated.
Purpose of the Study:
- To elucidate the functional role and molecular mechanisms of miR-1260b in non-small cell lung cancer.
- To determine the relationship between miR-1260b expression and clinicopathological features of NSCLC.
- To explore miR-1260b as a potential diagnostic biomarker and therapeutic target for NSCLC.
Main Methods:
- Quantitative real-time PCR to measure miR-1260b expression in NSCLC samples and cell lines.
- Cell proliferation, cell cycle, apoptosis, and senescence assays to assess functional impact.
- Luciferase reporter assays and Western blotting to confirm direct targeting of SOCS6 and downstream signaling.
- Analysis of correlations between miR-1260b expression and clinical data.
Main Results:
- miR-1260b was significantly upregulated in NSCLC plasma, tissues, and cell lines, correlating with tumor size and progression.
- Overexpression of miR-1260b promoted NSCLC cell proliferation and cell cycle progression while inhibiting apoptosis and senescence.
- miR-1260b directly targeted SOCS6, leading to its suppression and subsequent activation of KIT signaling.
- YY1 was identified as an upstream regulator of miR-1260b.
Conclusions:
- This study is the first to demonstrate that miR-1260b, regulated by YY1, promotes NSCLC progression by targeting SOCS6 and activating KIT signaling.
- miR-1260b plays a critical role in regulating NSCLC cell proliferation and apoptosis.
- miR-1260b represents a promising biomarker and therapeutic target for non-small cell lung cancer.
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