Prostate cancer (PC) is a common malignancy and is one of the leading causes of cancer-related death in men worldwide. Wang et al. categorized PC as the fifth-most commonly detected malignancy, with an estimated 1,414,000 new cases and 375,304 deaths in men globally [1]. Osteosarcoma (OS) is the most common bone cancer, representing 20–40% of all bone malignancies cases [2]. While primary bone malignancy is rare in adults, it is more common in children and youths, accounting for 3–5% of all cancers in that age group compared to 1% of all cancer cases in adults [3,4]. Moreover, the average five-year overall survival is 80% for individuals with a localized OS. However, patients with metastatic bone carcinoma have an even lower survival rate [4]. Cancer metastasis is a cascade of processes by which cancer cells separate from the primary tumor site and migrate to distant tissues or organs through the blood circulation or lymphatic system to colonize and form secondary tumors. Along with angiogenesis, epithelial-mesenchymal transition (EMT), hypoxia, and other mechanisms, several tumor microenvironment factors contribute to this process. The metastatic cascade involves invasion, intravasation, circulation survival, extravasation, and colonization of a distant tissue [5,6]. The metastasis cascade starts at the primary tumor site, where cancer cells detach by recruiting different proteases to destroy the extracellular matrix and invade the surrounding tissue. Next, cancer cells undergo EMT, gain highly invasive characteristics, intravasate through blood or lymphatic vessels, and migrate via the circulatory or lymphatic systems. Then, the metastatic cells attach to blood or lymphatic vessels’ internal lining to extravasate into the target organs. When these cells arrive at their distinct organ, they undergo a mesenchymal-epithelial transition (MET) that disrupts the new microenvironment to their advantage, beginning colonization [5,7].

More than 90% of patients diagnosed with advanced PC show evidence of bone metastasis [8]. Generally, PC is incurable once it has reached the bone [9]. According to the seed and soil hypothesis, metastasis is an organ-specific process depending on the interactions between disseminated tumor cells “seeds” and the host organs “soil”. Therefore, PC has a high affinity to metastasize to bone more than to other sites [7,9]. There are several factors that play a major role in allowing PC to attach and survive practically in bone. These factors include vascular properties and elevated blood flow in the red marrow [10], and the presence of adhesion molecules that are secreted by the tumor cells allowing these cells to bind to the bone marrow cells. This interaction between PC and bone cells results in activating bone anabolic pathways classically described as a “vicious cycle” [11]. In brief, PC cells tend to modify the surrounding microenvironment by secreting molecules that enhance osteoblast differentiation and proliferation such as transforming growth factor beta (TGF-β) and endothelin-1 [12,13]. On the other hand, activated osteoblasts drive tumor progression by releasing different other growth factors, including insulin-like growth factors (IGFs) and interleukins 6 and 8 [14,15]. The effect of PC cells is not limited only to osteoblasts; they also activate osteoclastogenesis through pro-osteolytic factors, thus resulting in bone resorption by releasing more TGF- and IGF-1 to support the tumor growth [16]. Moreover, these growth factors secreted from the bone microenvironment aid in regulating EMT/MET in tumor cells and facilitate their migration into a new microenvironment and establishing growing lesions in metastatic sites, respectively [17,18,19]. In young patients, OS develops from mesenchymal cells at the bone with abnormal growth [20]. Although the majority of OS cells exhibit an epithelial or hybrid mesenchymal and epithelial phenotype, EMT and MET events are frequently observed and regulated by many molecular players [21], similar to those observed in PC.

Most human RNA transcripts are now known to be noncoding. While 70–90% of the human genome is transcribed into RNA, only ~2% encodes proteins [22]. Transcribed RNAs that do not encode proteins are called noncoding RNAs (ncRNAs). These ncRNAs, including long ncRNAs (lncRNAs), are generally involved in several biological processes, have significant biological importance in regulating genes through transcriptional or post-transcriptional processes, and are involved in the pathogenesis of various human diseases including many types of cancer. NcRNAs can be broadly classified into three groups based on their length: <40 nucleotides, 40–200 nucleotides, and >200 nucleotides (i.e., lncRNAs) [5,23]. LncRNAs are RNA transcripts 200–100,000 nucleotides in length that were first extracted from eukaryotic cells and found mainly in the cytoplasm and nucleus [6,23,24]. Volders et al. identified approximately 127,802 putative lncRNAs encoded in the human genome [25]. There are currently more than 100,000 reported associations between human lncRNAs and diseases, molecular interactions, and drugs [26].

2. Oncogenic lncRNAs in PC and OS Malignancy

3.1. Differentiation Antagonizing Non-Protein Coding RNA