Long Non-Coding RNAs: Role in Testicular Cancers

Abstract

In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such as secondary tumors, infertility, and cardiovascular diseases. It is therefore important to study the impact of lncRNAs in the tumorigenesis of testicular cancer in order to learn how to exploit them in a clinical setting and to substitute more toxic treatments. Eventually, the use of lncRNAs as biomarkers, drug targets, or therapeutics for testicular cancer may represent a valid alternative to that of conventional tools, leading to a better management of this malignancy and its related conditions, and possibly even to the treatment of poor prognosis cases.

Keywords: hypogonadism; non-seminomas; seminomas; testicular germ-cell tumors; testis cancer.

Figure 1

Schematic representation of non-coding RNAs (ncRNAs) of different lengths. Short non-coding RNAs (sncRNAs) are shorter than 200 nucleotides (nts). Among them one can find miRNAs (22 nts), piRNAs (26–31 nts), snoRNAs (60–140 nts), and snRNAs (~150 nts). On the other hand, long non-coding RNAs (lncRNAs) are longer than 200 nts, reaching up to thousands of nts of length.

Figure 2

Schematic representation of long non-coding RNAs (lncRNAs) different molecular mechanisms. (A) Decoy lncRNAs titrate away proteins or miRNAs from their molecular partners, inhibiting their function. (B) Guide lncRNAs bind protein partners and direct them toward a specific cellular compartment or genomic target. (C) Allosteric lncRNAs interact with transcription factors or enzymes causing structural modifications that modify their activity. (D) Scaffold lncRNAs bind different molecular partners (proteins or RNAs) allowing them to interact or assemble into a complex. (E) Signaling lncRNAs are transcribed following a stimulus for which they act as signal molecules. They can be packed in exosomes and transmitted to other cells. (F) Precursor lncRNAs are processed into miRNAs or translated into functional micropeptides.

Figure 3

Role of different lncRNA in testicular cancer pathogenesis. Testicular cancer cells proliferation is promoted by lncRNA HOTTIP and SPRY4-IT1, while it is inhibited by NCL1-C, which also drives testicular cancer cells apoptosis. Cisplatin-based treatments resistance can be promoted by the H19/TDRG1 pathway, since H19 is able to upregulate TDRG1, which in turn triggers therapy resistance. Finally, testicular tumor invasiveness is promoted by SPRY4-IT1, which not only increases the cell proliferative rate, but also their motility and invasiveness.