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Updated: Apr 11, 2026
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Alterations in microRNAs miR-21 and let-7a correlate with aberrant STAT3 signaling and downstream effects during
Gauri Shishodia1,2,3, Shirish Shukla4,5, Yogesh Srivastava6
1Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, I - 7, Sector -39, Noida, 201301, Uttar Pradesh, India. gaurishishodia@gmail.com.
Background:
Present study provides clinical evidence of existence of a functional loop involving miR-21 and let-7a as potential regulators of aberrant STAT3 signaling recently reported by our group in an experimental setup (Shishodia et al. BMC Cancer 2014, 14:996). The study is now extended to a set of cervical tissues that represent natural history of human papillomavirus (HPV)-induced tumorigenic transformation.
Materials And Methods:
Cervical tissues from histopathologically-confirmed pre-cancer (23) and cancer lesions (56) along with the normal control tissues (23) were examined for their HPV infection status, expression level of miR-21 & let-7a and STAT3 & pSTAT3 (Y705) by PCR-based genotyping, quantitative real-time PCR and immunoblotting.
Results:
Analysis of cancer tissues revealed an elevated miR-21 and reduced let-7a expression that correspond to the level of STAT3 signaling. While miR-21 showed direct association, let-7a expression was inversely related to STAT3 expression and its activation. In contrast, a similar reciprocal expression kinetics was absent in LSIL and HSIL tissues which overexpressed let-7a. miR-21 was found differentially overexpressed in HPV16-positive lesions with a higher oncoprotein E6 level. Overexpression of miR-21 was accompanied by elevated level of other STAT3-regulated gene products MMP-2 and MMP-9. Enhanced miR-21 was found associated with decreased level of STAT3 negative regulator PTEN and negative regulator of MMPs, TIMP-3.
Conclusion:
Overall, our study suggests that the microRNAs, miR-21 and let-7a function as clinically relevant integral components of STAT3 signaling and are responsible for maintaining activated state of STAT3 in HPV-infected cells during cervical carcinogenesis.
Insights
MicroRNAs miR-21 and let-7a are key regulators of STAT3 signaling in cervical cancer. Their altered expression is linked to human papillomavirus (HPV) infection and disease progression.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Aberrant Signal Transducer and Activator of Transcription 3 (STAT3) signaling is implicated in cervical carcinogenesis.
- Our previous work established a functional loop involving miR-21 and let-7a in experimental models.
- This study investigates these microRNAs in clinical cervical tissue samples representing the natural history of human papillomavirus (HPV)-induced transformation.
Purpose of the Study:
- To provide clinical evidence for the role of miR-21 and let-7a in regulating STAT3 signaling in HPV-associated cervical lesions.
- To correlate microRNA expression with STAT3 activation and HPV status in cervical tissues.
Main Methods:
- Analysis of cervical tissues (normal, pre-cancer, cancer) for HPV status, miR-21, let-7a, STAT3, and pSTAT3 expression.
- Techniques included PCR-based genotyping, quantitative real-time PCR, and immunoblotting.
Main Results:
- Cervical cancer tissues showed elevated miR-21 and reduced let-7a, correlating with STAT3 activation.
- miR-21 expression was directly associated with STAT3, while let-7a was inversely related.
- miR-21 overexpression was observed in HPV16-positive lesions and linked to increased MMP-2/9 and decreased PTEN/TIMP-3 levels.
Conclusions:
- miR-21 and let-7a are clinically relevant components of STAT3 signaling in cervical carcinogenesis.
- These microRNAs contribute to maintaining STAT3 activation in HPV-infected cervical cells.
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