# Investigating the Relationship Between Long Non-Coding RNAs and miR-200 Family Expression in Clear Cell Renal Cell Carcinoma

## TL;DR

This study explores how long non-coding RNAs influence the miR-200 family in kidney cancer, suggesting new biomarkers and treatment approaches.

## Contribution

The study identifies specific lncRNAs that correlate with miR-200 family expression in RCC, offering new insights into regulatory mechanisms.

## Key findings

- 127 lncRNAs with regulatory functions were identified, 31 validated in RCC samples.
- Three lncRNAs (MALAT1, OIP5-AS1, LINC00467) correlated with all miR-200 family members.
- Downregulation of miR-200 family and lncRNAs was observed in carcinoma tissues.

## Abstract

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins and primarily serve regulatory functions. They are categorized by length into small ncRNAs (e.g., microRNAs) and long non-coding RNAs (lncRNAs). The microRNAs of the miR-200 family are well-known inhibitors of epithelial-to-mesenchymal transition (EMT). In our previous studies, we observed miR-200 family downregulation in renal cell carcinoma (RCC). However, there is limited data regarding the regulation of miR-200 family expression by lncRNAs in RCC. Our results indicate that miR-200 family expression in RCC correlates at least in part with the expression of lncRNAs. This work emphasizes the significance of the complex network of different classes of ncRNAs that may contribute to the development of RCC and could be crucial for establishing new biomarkers and for developing new treatment modalities for advanced, incurable forms of RCC.

Objectives: MicroRNAs of the miR-200 family are recognized as key inhibitors of epithelial-to-mesenchymal transition (EMT). However, there is limited data on the potential regulation of miR-200 family expression by long non-coding RNAs (lncRNAs) in RCC. Methods: We conducted a comprehensive literature and database search to identify lncRNAs that had been already functionally validated as regulators of any member of the miR-200 family. We analyzed the expression levels of the miR-200 family and the identified lncRNAs by qPCR. The study included 42 samples of carcinoma and non-carcinoma tissue from 25 RCC patients. In addition, we used RNA sequencing data from The Cancer Genome Atlas (TCGA), encompassing 511 kidney RCC (KIRC) samples, to further analyze the expression of miRNAs and lncRNAs. Results: We identified 127 lncRNAs with confirmed regulatory functions, 31 of which were validated in our samples. The majority of lncRNAs, along with all members of the miR-200 family, showed consistent downregulation in carcinoma tissues compared to non-carcinoma tissues. We observed a significant correlation between the expression of at least one member of the miR-200 family and 17 lncRNAs. In particular, three lncRNAs (MALAT1, OIP5-AS1, and LINC00467) showed a correlation with the expression of all members of the miR-200 family. Our results were at least partially confirmed in KIRC samples from the TCGA dataset. Conclusions: Our results suggest that the expression of the miR-200 family in RCC might be at least partially influenced by lncRNAs. Based on our cohort of samples, MALAT1, OIP5-AS1, and LINC00467 appear to be potentially important contributors to RCC development.