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Long Non-coding RNAs in Pulmonary Neuroendocrine Neoplasms
Damodaran Narayanan1, Rakesh Mandal1, Heather Hardin1
1Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53792-8550, USA.
Endocrine Pathology
|May 11, 2020
Summary
Insulinoma-associated protein 1 (INSM1) accurately identifies pulmonary neuroendocrine neoplasms (NENs), including poorly differentiated types. Long non-coding RNAs (lncRNAs) like HOTAIR, MEG3, and PCA3 show higher expression in aggressive NENs, suggesting prognostic and therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Pulmonary neuroendocrine neoplasms (NENs) require precise classification due to differing therapeutic strategies.
- Challenges in NEN diagnosis include overlapping histological features and reduced neuroendocrine marker expression in high-grade neuroendocrine carcinomas (NECs).
- Insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for neuroendocrine differentiation.
Purpose of the Study:
- To evaluate INSM1 as a sensitive diagnostic marker for pulmonary NENs, particularly poorly differentiated NECs.
- To characterize the expression and functional role of specific long non-coding RNAs (lncRNAs) in various pulmonary NEN subtypes.
- To explore the potential of lncRNAs as prognostic indicators and therapeutic targets for pulmonary NENs.
Main Methods:
- Immunohistochemistry was used to detect INSM1 expression in pulmonary NENs.
- In situ hybridization and real-time polymerase chain reaction were employed to quantify lncRNA expression (HOTAIR, MEG3, PCA3) across NEN subtypes.
- Small interfering RNA (siRNA) was utilized to investigate the functional role of MEG3 and PCA3 in tumor proliferation.
Main Results:
- INSM1 expression was detected in over 94% of pulmonary NENs, confirming its high sensitivity and utility for identifying poorly differentiated NECs.
- Higher expression of HOTAIR, MEG3, and PCA3 was observed in small cell lung carcinoma (SCLC/NEC) compared to other NEN subtypes (p < 0.01).
- MEG3 and PCA3 knockdown using siRNA demonstrated a role in regulating tumor cell proliferation.
Conclusions:
- INSM1 is a highly sensitive immunohistochemical marker for diagnosing pulmonary NENs, aiding in the identification of challenging cases.
- Specific lncRNAs (HOTAIR, MEG3, PCA3) are differentially expressed in pulmonary NEN subtypes, with elevated levels in aggressive forms.
- These lncRNAs represent potential prognostic biomarkers for NEN aggressiveness and novel therapeutic targets.
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