Long Non-Coding RNAs as Novel Biomarkers in the Clinical Management of Papillary Renal Cell Carcinoma Patients: A Promise or a Pledge?

Abstract

Papillary renal cell carcinoma (pRCC) represents the second most common subtype of renal cell carcinoma, following clear cell carcinoma and accounting for 10–15% of cases. For around 20 years, pRCCs have been classified according to their mere histopathologic appearance, unsupported by genetic and molecular evidence, with an unmet need for clinically relevant classification. Moreover, patients with non-clear cell renal cell carcinomas have been seldom included in large clinical trials; therefore, the therapeutic landscape is less defined than in the clear cell subtype. However, in the last decades, the evolving comprehension of pRCC molecular features has led to a growing use of target therapy and to better oncological outcomes. Nonetheless, a reliable molecular biomarker able to detect the aggressiveness of pRCC is not yet available in clinical practice. As a result, the pRCC correct prognosis remains cumbersome, and new biomarkers able to stratify patients upon risk of recurrence are strongly needed. Non-coding RNAs (ncRNAs) are functional elements which play critical roles in gene expression, at the epigenetic, transcriptional, and post-transcriptional levels. In the last decade, ncRNAs have gained importance as possible biomarkers for several types of diseases, especially in the cancer universe. In this review, we analyzed the role of long non-coding RNAs (lncRNAs) in the prognosis of pRCC, with a particular focus on their networking. In fact, in the competing endogenous RNA hypothesis, lncRNAs can bind miRNAs, resulting in the modulation of the mRNA levels targeted by the sponged miRNA, leading to additional regulation of the target gene expression and increasing complexity in the biological processes.

The Roles of Ferroptosis-related Long Non-coding RNAs in Urologic Cancers

“…Silencing lncRNA SLC16A1-AS1 induced ferroptosis in ccRCC through miR-143-3p/ SLC7A11 signaling [26]. In PRCC, frlncRNAs have been shown to interact with sponge miRNAs and bind proteins to modulate cell proliferation and metastasis [27]. In BCa, LncRNA RP11-89 promotes tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p [28].…”

The Clinical and Molecular Features in the VHL Renal Cancers; Close or Distant Relatives with Sporadic Clear Cell Renal Cell Carcinoma?

“…In fact, the creation of a new molecular panel of circulating predictive biomarkers could help physicians to immediately highlight patients with a high predisposition of ccRCC development to follow a precise new medical algorithm able to detect and eliminate renal neoplasms at early stages with minimally invasive techniques, such as thermal or cryo-ablations, with the maximum saving of renal parenchyma over time [ 130 ]. In the molecular scenario, non-coding RNAs represent one of the most promising classes of predictive biomarkers in several types of malignancies and chronic conditions [ 131 , 132 ]. Non-coding RNAs are regulatory RNAs with no or little protein-coding potential [ 133 ].…”

Construction of a cuproptosis‐related lncRNA signature for predicting prognosis and immune landscape in osteosarcoma patients

“… 19 , 20 , 21 Due to the characteristics of tissue specificity, high stability, abundance, and species conservation, lncRNAs have been identified as a possible diagnostic and prognostic biomarker in the clinical management of cancer. 22 Additionally, lncRNAs are also associated with tumor metabolism, tumor microenvironment, and drug resistance, 23 consequently recognized as potential cancer drug targets. 24 , 25 …”

“…[19][20][21] Due to the characteristics of tissue specificity, high stability, abundance, and species conservation, lncRNAs have been identified as a possible diagnostic and prognostic biomarker in the clinical management of cancer. 22 Additionally, ln-cRNAs are also associated with tumor metabolism, tumor microenvironment, and drug resistance, 23 consequently recognized as potential cancer drug targets. 24,25 Programmed cell death is an essential physiological and pathological process to remove superfluous or damaged cells to ensure healthy development and tissue homeostasis, 26 including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis.…”

“…Numerous studies have observed that the mutations and dysregulations in the lncRNAs cause many human diseases, such as cerebrovascular diseases, 15 ischemic injuries, 16 endocrinologies, 17 immune system diseases, 18 and especially cancer 19–21 . Due to the characteristics of tissue specificity, high stability, abundance, and species conservation, lncRNAs have been identified as a possible diagnostic and prognostic biomarker in the clinical management of cancer 22 . Additionally, lncRNAs are also associated with tumor metabolism, tumor microenvironment, and drug resistance, 23 consequently recognized as potential cancer drug targets 24,25 …”