Non-coding RNAs in drug and radiation resistance of bone and soft tissue sarcoma: a systematic review

Background: Sarcomas comprise approximately 1% of all human malignancies; treatment resistance is one of the major reasons for the poor prognosis of sarcomas. 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 the PubMed (MEDLINE) database for articles regarding sarcoma-associated non-coding RNAs from inception to August17, 2022. Studies investigating the roles of host-derived microRNAs, long non-coding RNAs, and circular RNAs in sarcoma were included. Data regarding the roles of ncRNAs in therapeutic regulation and their applicability as biomarkers for predicting therapeutic response of sarcomas were extracted. Two independent researchers assessed the quality of the studies using Würzburg Methodological Quality Score(W-MeQS).

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, W-MeQS scores ranged from 3 to 10 (average score = 5.42). Of the twelve 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 for predicting treatment response and therapeutics for sarcoma, their differential expression across tissues complicates their application. Further research regarding their potential for inhibiting or activating these regulatory molecules to reverse treatment resistance may be useful.

Funding: This study's literature retrieval cost was supported by the 345 Talent Project of Shengjing Hospital of China Medical University(M0949 to Tao Zhang).