LncRNAs and the Angiogenic Switch in Cancer: Clinical Significance and Therapeutic Opportunities

Abstract

Angiogenesis is one of the hallmarks of cancer, and the establishment of new blood vessels is vital to allow for a tumour to grow beyond 1–2 mm in size. The angiogenic switch is the term given to the point where the number or activity of the pro-angiogenic factors exceeds that of the anti-angiogenic factors, resulting in the angiogenic process proceeding, giving rise to new blood vessels accompanied by increased tumour growth, metastasis, and potential drug resistance. Long noncoding ribonucleic acids (lncRNAs) have been found to play a role in the angiogenic switch by regulating gene expression, transcription, translation, and post translation modification. In this regard they play both anti-angiogenic and pro-angiogenic roles. The expression levels of the pro-angiogenic lncRNAs have been found to correlate with patient survival. These lncRNAs are also potential drug targets for the development of therapies that will inhibit or modify tumour angiogenesis. Here we review the roles of lncRNAs in regulating the angiogenic switch. We cover specific examples of both pro and anti-angiogenic lncRNAs and discuss their potential use as both prognostic biomarkers and targets for the development of future therapies.

RNA Modifications Meet Tumors

“… 25 , 101 , 104 , 105 , 179 When the surrounding nutrients are exhausted, tumors can generate blood vessels under the regulation of RNA modifications, which can connect them with the vascular system (blood vessels and lymph vessels) and membrane blood vessels in the human body to obtain energy and other materials elsewhere or be carried to obtain a better living environment in the distance. 123 , 128–132 Furthermore, tumor and immune cells in the tumor microenvironment can form a cell-cell “internet”, and immune cells that should protect the human body help tumor cells grow and metastasize well with the participation of RNA modifications. Therefore, RNA modifications are vital in many aspects of tumor cell growth and development.…”

“…Newborn blood vessels can provide energy to tumors, promote tumor growth and metastasis, and lead to drug resistance and recurrence. 128 , 129 Moreover, the employment of anti-angiogenesis drugs is becoming a new method of tumor therapy, aiming to cause less harm to tumor patients and have a better prognosis than traditional therapy. 130 The role of RNA modifications in angiogenesis has also gradually been recognized.…”

Progress in the research of cuproptosis and possible targets for cancer therapy

“…Using in situ hybridization and real-time quantitative PCR, Mabeta et al [ 30 ] investigated the differential expression of the LIAS gene in normal lung tissue and lung cancer samples. Their findings suggest that alteration in LIAS expression levels can promote lung cancer development, making LIAS an attractive target for novel therapies[ 29 ].…”

The VEGF/VEGFR Axis Revisited: Implications for Cancer Therapy

“…In the normal physiological setting, the balance between angiogenesis inhibitors and stimulators is intricately controlled [ 3 , 4 ]. On the flip side, the loss of balance between pro- and anti-angiogenic molecules promotes the transition from dormancy to malignancy [ 3 , 5 , 6 ]. As a result, research has focused on identifying factors that regulate angiogenesis and on understanding their behavior in the tumor setting [ 7 ].…”