Long non-coding RNAs and cellular interactions : investigating underlying mechanisms of oncogenesis

Cancer is a leading cause of death worldwide with one in 8 men and one in 11 women dying from the disease (World Health Organization, 2018). Despite vast improvements in cancer diagnosis and therapy, the global cancer burden continues to rise in unison with population growth and longevity. Although cancer presents itself as a heterogeneous group of diseases, often divided by tissue of origin, tumor characterization increasingly identifies molecular level commonalities and patterns that are similar across all cancers. Expanding our knowledge of these molecular characteristics, together with the development of new tools and technologies, has historically been one of the most efficient ways to increase the effectivity of cancer therapies and thus, decrease the cancer burden of the population. This thesis investigates two newly identified molecular mechanisms, long non-coding RNAs and cell-cell interactions, whose role are increasingly appreciated in tumor progression and development. In addition, the thesis reports the development of methods and tools that have been established to facilitate further investigation of cancers molecular attributes by the scientific community.

List of scientific papers

I. Serviss, J. T.*, Gådin, J. R.*, Eriksson, P., Folkersen, L., Grandér, D. (2017). ClusterSignificance: A bioconductor package facilitating statistical analysis of class cluster separations in dimensionality reduced data. Bioinformatics. 33(19), 3126-3128. *Equal contribution.
https://doi.org/10.1093/bioinformatics/btx393

II. Serviss, J. T., Andrews, N., Van den Eynden, J., Richter, F. C., Houtman, M., Vesterlund, M., Schwarzmueller, L., Johnsson, P., Larsson, E., Grandér, D., Pokrovskaja Tamm, K. (2018). An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a. Cell Death and Disease. 9(736).
https://doi.org/10.1038/s41419-018-0777-5

III. Serviss, J.T.*, Andrews, N.*, Andersson, A.B., Dzwonkowska, E., Heijboer, R., Gerling, M. & Enge, M. Unsupervised cell interaction profiling based on multiplet RNA sequencing reveals major architectural differences between small intestinal and colonic epithelium. *Equal contribution. [Manuscript]