Altered expression of microRNA miR‐21, miR‐155, and let‐7a and their roles in pulmonary neuroendocrine tumors

Abstract

MicroRNA (miRNA) has a critical effect on tumorigenesis through post-transcriptional modification and is considered to be potential biomarkers for cancer diagnosis and treatment monitoring. We evaluated the expression pattern of three selected miRNAs (miR-21, miR-155, and let-7a) to evaluate their potential roles by quantitative reverse transcription-polymerase chain reaction using formalinfixed and paraffin-embedded tissues of 63 surgically resected pulmonary neuroendocrine (NE) tumors (19 typical carcinoids (TCs), 6 atypical carcinoids (ACs), 19 large cell NE carcinomas (LCNECs), and 19 small cell lung carcinomas (SCLCs). Control amplification for U6 small nuclear RNA (U6) was performed in all samples. Normalized Ct values were calculated (CtExperimental miRNA-CtU6) for each case and recorded. The expression levels of miR-21 and miR-155 were significantly higher in high-grade NE carcinomas (LCNECs and SCLCs) than in carcinoid tumors (TCs and ACs) (each P < 0.001). The expression level of miR-21 in carcinoid tumors with lymph node metastasis was significantly higher than in carcinoid tumors without lymph node metastasis (P = 0.010). To the best of our knowledge, the present study is the first to examine the expression patterns of miR-21 and miR-155 as an adjunctive diagnostic tool or clinically relevant biomarkers for pulmonary NE tumors.

Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study

“…1,2 Pulmonary neuroendocrine tumors form a distinct group of neoplasms that share characteristic morphological, immunohistochmical, ultrastructural and molecular features. 3 These tumors considerably differ in their biological behaviors, thus, they are classified as either low-grade typical carcinoids, intermediate-grade atypical carcinoids, high-grade large cell neuroendocrine lung cancer, or small cell lung cancer. 3,4 Small cell lung cancers account for the largest group of these tumors (B15% of all lung malignancies) and are associated with an extremely poor prognosis, [5][6][7][8] whereas large cell euroendocrine cancers and carcinoids are rare.…”

“…3 These tumors considerably differ in their biological behaviors, thus, they are classified as either low-grade typical carcinoids, intermediate-grade atypical carcinoids, high-grade large cell neuroendocrine lung cancer, or small cell lung cancer. 3,4 Small cell lung cancers account for the largest group of these tumors (B15% of all lung malignancies) and are associated with an extremely poor prognosis, [5][6][7][8] whereas large cell euroendocrine cancers and carcinoids are rare. Currently, the 2004 World Health Organization classification of pulmonary neuroendocrine tumors is based on combined architectural patterns considering the two most relevant morphological parameters, that is, the mitotic index and the presence of necrosis, diagnosed by haematoxylin and eosin morphology.…”

“…Currently, the 2004 World Health Organization classification of pulmonary neuroendocrine tumors is based on combined architectural patterns considering the two most relevant morphological parameters, that is, the mitotic index and the presence of necrosis, diagnosed by haematoxylin and eosin morphology. 3,8,9 However, these tumors represent a broad spectrum of phenotypically distinct entities, and the assignment of a given neuroendocrine lung tumor can occasionally be cumbersome even for experienced pathologists. 3,9,10 Thus, reproducible and objective (molecular) diagnostic criteria with clinical and prognostic value need to be established to achieve a more accurate assignment of the various types of pulmonary neuroendocrine tumors.…”

“…3,8,9 However, these tumors represent a broad spectrum of phenotypically distinct entities, and the assignment of a given neuroendocrine lung tumor can occasionally be cumbersome even for experienced pathologists. 3,9,10 Thus, reproducible and objective (molecular) diagnostic criteria with clinical and prognostic value need to be established to achieve a more accurate assignment of the various types of pulmonary neuroendocrine tumors. 3 Micro-RNA (miRNA) molecules are evolutionarily conserved, small RNA-molecules with a size of 19-24 nucleotides and, unlike mRNA, do not encode amino-acid sequences.…”

“…3,9,10 Thus, reproducible and objective (molecular) diagnostic criteria with clinical and prognostic value need to be established to achieve a more accurate assignment of the various types of pulmonary neuroendocrine tumors. 3 Micro-RNA (miRNA) molecules are evolutionarily conserved, small RNA-molecules with a size of 19-24 nucleotides and, unlike mRNA, do not encode amino-acid sequences. 3,11,12 miRNAs function as negative endogenous gene-expression regulators by binding complementary sequences in target mRNAs, resulting in their selective degradation or selective steric inhibition of translation.…”