Down-regulation of Halr1 during induced differentiation of embryonal carcinoma P19 cells

Maintenance of pluripotency depends to diverse regulatory factors.Studies in embryonic stem cells(ESCs)have indicated that large intergenic non-coding RNAs(lincRNAs)are involved in the regulatory network of pluripotency.However,the presence and function of pluripotency-associated lincRNAs in cancer cells with pluripotency features are unknown.In this study,we used embryonal carcinoma(EC)P19 cell lines to investigate the expression level of Halr1 in pluripotency and retinoic acid(RA)-induced differentiated states.Down-regulation of pluripotency associated factors such as OCT4,NANOG,SSEA1 and alkaline phosphatase at transcript and protein levels were used to confirm the differentiated status of P19 cells.Quantitative measurement of Halr1 transcript levels revealed a 79% decrease during RA-induced differentiation of P19 cells.These results indicate that upon exiting the pluripotency state the expression level of Halr1 similar to core pluripotency factors is remarkably reduced.

Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.