Functions And Mechanisms Study Of Microprotein Encoded By LINC00998 Inhibiting Unfolded Protein Pathway To Promote Growth Of Cervical Cancer Cell

Approximately 97% of RNA in the human transcriptome is non-coding RNA.Advances in next-generation sequencing,bioinformatics,and mass spectrometry have revealed new insights into the role and function of ncRNAs,including their potential to encode functional micropeptides.A large number of genes originally defined as noncoding RNAs can also encode microproteins or proteins and play important roles in a variety of physiological functions and human diseases and cancers.But much is still unknown about the functional mechanism of this hidden group of microproteins or proteins.lncRNAs are generally defined as ncRNAs with a length of more than 200 nucleotides(nt),which account for the largest proportion in the mammalian noncoding transcriptome,once considered to be nonfunctional relics of evolution,are emerging as essential genes in tumor progression.Cervical cancer is one of the most common malignant tumors in gynecology.Globally,cervical cancer is the fourth most common cancer and one of the most common cancers in developing countries.Cervical cancer poses a huge health threat to women.This study aims to explore the mechanism of the microprotein encoded by non-coding RNA LINC00998 in the progression of cervical cancer.Through GEPIA database screening,we find that LINC00998 is significantly upregulated in cervical cancer tissues,and the high expression of LINC00998 is associated with poor prognosis lines.Functional experiments shows that knockdown of LINC00998 inhibits the proliferation and migration of cervical cancer cells in vitro,while overexpression of LINC00998WT(encodeable form)enhanced the growth of cervical cancer cells,while LINC00998MUT(unencodeable form)showed no such effect.Further mechanism studies shows that after knocking down LINC00998,ER stress is enhanced,and the unfolded protein response pathway is significantly activated,which ultimately promotes ER stress-mediated apoptosis.In vivo tumorigenesis experiments in nude mice also shows that knockdown of LINC00998 could significantly inhibit tumorigenesis in cervical cancer cells.In conclusion,our results confirms that the microprotein encoded by LINC00998 is a new type of cervical cancer promoting factor,which is involved in the processing and folding process of ER proteins,regulates ER stress,and mediates the growth of cancer cells through ER stress,indicating that this microprotein may be a new type of therapeutic target.