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Updated: Oct 2, 2025
Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells
Published on: June 16, 2023
A genome-wide expression profile of noncoding RNAs in human osteosarcoma cells as they acquire resistance to
Harshita Sharma1, Divya Niveditha1, Rajdeep Chowdhury1
1Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani, Rajasthan, 333031, India.
Background:
Recurrence after cisplatin therapy is one of the major hindrances in the management of cancer. This necessitates a deeper understanding of the molecular signatures marking the acquisition of resistance. We therefore modeled the response of osteosarcoma (OS) cells to the first-line chemotherapeutic drug cisplatin. A small population of nondividing cells survived acute cisplatin shock (persisters; OS-P). These cells regained proliferative potential over time re-instating the population again (extended persisters; OS-EP).
Result:
In this study, we present the expression profile of noncoding RNAs in untreated OS cells (chemo-naive), OS-P, OS-EP and drug-resistant (OS-R) cells derived from the latter. RNA sequencing was carried out, and thereafter, differential expression (log2-fold ± 1.5; p value ≤ 0.05) of microRNAs (miRNAs) was analyzed in each set. The core set of miRNAs that were uniquely or differentially expressed in each group was identified. Interestingly, we observed that most of each group had their own distinctive set of miRNAs. The miRNAs showing an inverse correlation in expression pattern with mRNAs were further selected, and the key pathways regulated by them were delineated for each group. We observed that pathways such as TNF signaling, autophagy and mitophagy were implicated in multiple groups.
Conclusion:
To the best of our knowledge, this is the first study that provides critical information on the variation in the expression pattern of ncRNAs in osteosarcoma cells and the pathways that they might tightly regulate as cells acquire resistance.
Insights
Chemotherapy resistance in osteosarcoma involves distinct noncoding RNA (ncRNA) profiles. Understanding these ncRNA variations and regulated pathways is crucial for overcoming treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Cisplatin resistance is a major challenge in osteosarcoma (OS) treatment.
- Understanding molecular mechanisms of resistance is critical for improving patient outcomes.
- A subpopulation of non-dividing osteosarcoma cells (persisters) survive cisplatin treatment.
Purpose of the Study:
- To investigate the noncoding RNA (ncRNA) expression profiles in chemo-naive, cisplatin-persister (OS-P), extended-persister (OS-EP), and drug-resistant (OS-R) osteosarcoma cells.
- To identify differentially expressed microRNAs (miRNAs) and their associated regulatory pathways in these distinct cellular states.
- To elucidate the role of ncRNAs in the acquisition of cisplatin resistance in osteosarcoma.
Main Methods:
- Osteosarcoma cell lines representing different treatment responses (chemo-naive, OS-P, OS-EP, OS-R) were established.
- RNA sequencing was performed to analyze the expression profiles of noncoding RNAs.
- Differential expression analysis of microRNAs (miRNAs) was conducted, followed by pathway analysis of inversely correlated miRNA-mRNA expression.
Main Results:
- Distinct sets of differentially expressed microRNAs (miRNAs) were identified in each osteosarcoma cell group.
- Key pathways, including TNF signaling, autophagy, and mitophagy, were implicated in multiple resistant cell populations.
- Specific miRNAs showed inverse correlation with messenger RNAs (mRNAs), suggesting regulatory roles in resistance.
Conclusions:
- This study provides the first comprehensive analysis of noncoding RNA variations in osteosarcoma cells during the acquisition of cisplatin resistance.
- The identified ncRNAs and associated pathways offer potential targets for overcoming treatment resistance in osteosarcoma.
- Understanding these molecular signatures is vital for developing novel therapeutic strategies against refractory osteosarcoma.
