Background: Sarcomas comprise approximately 1% of all human malignancies, and treatment resistance is one of the main reasons for poor prognosis. Accumulating evidence suggests that non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are important molecules involved in the crosstalk between resistance to chemotherapy, targeted therapy, and radiotherapy via various pathways.

Methods: We searched PubMed (MEDLINE) databases for articles on non-coding RNAs relevant to sarcoma from inception to November 30, 2021. Studies investigating the roles of host-derived microRNAs, long non-coding RNAs, and circular RNAs in sarcoma were included. Data on the roles of ncRNAs in therapeutic regulation and their applicability as biomarkers of sarcomas were extracted. Two independent researchers assessed the quality of the studies using modified guidelines from the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.

Results: Observational studies revealed ectopic expression of non-coding RNAs in sarcoma patients with different responses to antitumor treatments. Experimental studies have confirmed crosstalk between cellular pathways pertinent to chemotherapy, targeted therapy, and radiotherapy resistance. Of the included studies, the SYRCLE scores ranged from 3 to 6 (average score = 4.51). This finding suggested a moderate risk of bias. Of the ten articles that investigated non-coding RNAs as biomarkers, none included a validation cohort. Selective reporting of the sensitivity, specificity, and receiver operating curves was common.

Conclusion: Although non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sarcoma, their differential expression across tissues complicates their application. Further investigation of the potential for inhibition or activation of these regulatory molecules to reverse treatment resistance may be useful.

We searched for relevant articles in PubMed using Medical Subject Heading (MeSH), as follows: (non-coding RNA OR ncRNA OR long non-coding RNA OR lncRNA OR circular RNA OR circRNA OR microRNA OR miRNA) AND (sarcoma OR osteosarcoma OR chondrosarcoma OR synovial sarcoma OR leiomyosarcoma OR liposarcoma OR fibrosarcoma OR Kaposi's sarcoma OR rhabdomyosarcoma OR Ewing's sarcoma OR angiosarcoma OR hemangiosarcoma OR gastrointestinal stromal tumors) AND (drug resistance OR chemoresistance OR chemotherapy resistance OR radioresistance OR radiotherapy resistance OR immunotherapy OR resistance OR sensitivity). The period from inception until November 30, 2021 was included. There were no restrictions on the type of study or the language used.