Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemotherapy drug resistance is unknown.
C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins.
Control and tumor specific induced pluripotent stem cells were reprogrammed with 5 reprogramming factors, Klf-4, c-Myc, Oct-4, Sox-2, and Lin-28, using the messenger RNA reprogramming system.
Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in 'AML with maturation' (according to 2016 WHO classification of myeloid neoplasms and acute leukemia).
High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.
In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance.
In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer.
Knockdown of LIV-1 expression resulted in (i) decreased expression of cancer stem cell-related molecules such as LIN28 and ATP-binding cassette sub-family G member 2, (ii) decreased spheroid-forming ability, (iii) decreased migration, (iv) decreased incidence of tumor formation in nude mice, and (v) upregulation of miR-7 expression.
Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level.
Our findings therefore show a critical role for the REST-LIN28A axis in tumor aggression and suggest a causative relationship between REST loss and tumorigenicity in vivo.
Partial resection of the tumor was performed and histological findings revealed multilayered rosettes with LIN28A staining, but genetic analysis showed no amplification of the C19MC microRNA cluster at 19q14.32.
The tumour-suppressor let-7 microRNA family has also been shown to be universally down-regulated in malignant GCTs, because of abundant expression of the regulatory gene LIN28.