Characterization of polyploidy in cancer: Current status and future perspectives.

Various cancers frequently exhibit polyploidy, observed in a condition where a cell possesses more than two sets of chromosomes, which is considered a hallmark of the disease. The state of polyploidy often leads to aneuploidy, where cells possess an abnormal number or structure of chromosomes. Recent studies suggest that oncogenes contribute to aneuploidy. This finding significantly underscores its impact on cancer. Cancer cells exposed to certain chemotherapeutic drugs tend to exhibit an increased incidence of polyploidy. This occurrence is strongly associated with several challenges in cancer treatment, including metastasis, resistance to chemotherapy and the recurrence of malignant tumors. Indeed, it poses a significant hurdle to achieve complete tumor eradication and effective cancer therapy. Recently, there has been a growing interest in the field of polyploidy related to cancer for developing effective anti-cancer therapies. Polyploid cancer cells confer both advantages and disadvantages to tumor pathogenicity. This review delineates the diverse characteristics of polyploid cells, elucidates the pivotal role of polyploidy in cancer, and explores the advantages and disadvantages it imparts to cancer cells, along with the current approaches tried in lab settings to target polyploid cells. Additionally, it considers experimental strategies aimed at addressing the outstanding questions within the realm of polyploidy in relation to cancer.

Polyploidy and mTOR signaling: a possible molecular link.

Polyploidy is typically described as the condition wherein a cell or organism has more than two complete sets of chromosomes. Occurrence of polyploidy is a naturally occurring phenomenon in the body's development and differentiation processes under normal physiological conditions. However, in pathological conditions, the occurrence of polyploidy is documented in numerous disorders, including cancer, aging and diabetes. Due to the frequent association that the polyploidy has with these pathologies and physiological process, understanding the cause and consequences of polyploidy would be beneficial to develop potential therapeutic applications. Many of the genetic and epigenetic alterations leading to cancer, diabetes and aging are linked to signaling pathways. Nonetheless, the specific signaling pathway associated with the cause and consequences of polyploidy still remains largely unknown. Mammalian/mechanistic target of rapamycin (mTOR) plays a key role in the coordination between eukaryotic cell growth and metabolism, thereby simultaneously respond to various environmental inputs including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in the regulation of many fundamental cellular processes that range from protein synthesis to autophagy. Dysregulated mTOR signaling has been found to be implicated in various disease progressions. Importantly, there is a strong correlation between the hallmarks of polyploidy and dysregulated mTOR signaling. In this review, we explore and discuss the molecular connection between mTOR signaling and polyploidy along with its association with cancer, diabetes and aging. Additionally, we address some unanswered questions and provide recommendations to further advance our understanding of the intricate relationship between mTOR signaling and polyploidy.

The nexus of long noncoding RNAs, splicing factors, alternative splicing and their modulations.

The process of alternative splicing (AS) is widely deregulated in a variety of cancers. Splicing is dependent upon splicing factors. Recently, several long noncoding RNAs (lncRNAs) have been shown to regulate AS by directly/indirectly interacting with splicing factors. This review focuses on the regulation of AS by lncRNAs through their interaction with splicing factors. AS mis-regulation caused by either mutation in splicing factors or deregulated expression of splicing factors and lncRNAs has been shown to be involved in cancer development and progression, making aberrant splicing, splicing factors and lncRNA suitable targets for cancer therapy. This review also addresses some of the current approaches used to target AS, splicing factors and lncRNAs. Finally, we discuss research challenges, some of the unanswered questions in the field and provide recommendations to advance understanding of the nexus of lncRNAs, AS and splicing factors in cancer.