Deciphering the roles of non-coding RNAs in liposarcoma development: Challenges and opportunities for translational therapeutic advances.

Liposarcoma is one of the most prevalent forms of soft tissue sarcoma, and its prognosis is highly dependent on its molecular subtypes. Non-coding RNAs (ncRNAs) like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) can bind various cellular targets to regulate carcinogenesis. By affecting the expressions and activities of their downstream targets post-transcriptionally, dysregulations of miRNAs can alter different oncogenic signalling pathways, mediating liposarcoma progression. On the contrary, lncRNAs can sponge miRNAs to spare their downstream targets from translational repression, indirectly affecting miRNA-regulated oncogenic activities. In the past 15 years, multiple fundamental and clinical research has shown that different ncRNAs play essential roles in modulating liposarcoma development. Yet, there is a lack of an effective review report that could summarize the findings from various studies. To narrow this literature gap, this review article aimed to compare the findings from different studies on the tumour-regulatory roles of ncRNAs in liposarcoma and to understand how ncRNAs control liposarcoma progression mechanistically. Additionally, the reported findings were critically reviewed to evaluate the translational potentials of various ncRNAs in clinical applications, including employing these ncRNAs as diagnostic and prognostic biomarkers or as therapeutic targets in the management of liposarcoma. Overall, over 15 ncRNAs were reported to play essential roles in modulating different cellular pathways, including apoptosis, WNT/β-catenin, TGF-β/SMAD4, EMT, interleukin, and YAP-associated pathways to influence liposarcoma development. 28 ncRNAs were reported to be upregulated in liposarcoma tissues or circulation, whereas 11 were downregulated, making them potential candidates as liposarcoma diagnostic biomarkers. Among these ncRNAs, measuring the tissues or circulating levels of miR-155 and miR-195 was reported to help detect liposarcoma, differentiate liposarcoma subtypes, and predict the survival and treatment response of liposarcoma patients. Overall, except for a few ncRNAs like miR-155 and miR-195, current evidence to support the use of discussed ncRNAs as biomarkers and therapeutic targets in managing liposarcoma is mainly based on a single-center study with relatively small sample sizes or cell-based studies. Hence, more large-scale multi-center studies should be conducted to further confirm the sensitivity, specificity, and safety of ncRNAs as biomarkers and therapeutic targets. Instead of furthering investigation to confirm the translational values of all the discussed ncRNAs, which can be time- and cost-consuming, it would be more practical to focus on a few ncRNAs, including miR-155 and miR-195, to evaluate if they are sensitive and safe to be used as liposarcoma biomarkers and therapeutic agents or targets.