LncRNAs as Regulators of the STAT۳ Signaling Pathway in Cancer

Cancer is a disorder of growth control and cell differentiation caused by the abnormal expression of multiple genes. Long non-coding RNAs (lncRNAs) are critical regulators of numerous biological processes, especially in the development of diseases. Abnormal expression of some lncRNAs causes disease, especially cancer, and disease resistance. lncRNAs may act as oncogenes or tumor suppressors and can be used as diagnostic or prognostic markers, and may also have therapeutic potential in cancer treatment. Studies show that many lncRNAs have different effects on cell activity by regulating multiple downstream targets, such as signaling pathways that are signal transducers and activators of transcription ۳ (STAT۳). The STAT۳ signaling pathway is one of the most critical pathways in developing various diseases, including cancer, which plays a vital role in cellular processes, disease onset and progression, and stem cell regeneration by regulating its target genes. STAT۳ has been proven to be an anticancer target in various contexts. Types of genes can activate the STAT۳ pathway in cancer. Many lncRNAs have been identified associated with the STAT۳ pathway that is upstream or downstream. Oncogenic lncRNAs, including PVT۱, HOTAIRM۱, and MCM۳AP-AS۱, increase STAT۳ expression, while tumor suppressor lncRNAs, such as TSLNC۸, TPTEP۱, and DILC decrease STAT۳ expression. These lncRNAs can affect STAT۳ signaling activity through numerous molecular mechanisms, including sponge of microRNAs, transcriptional activation/inhibition, and epigenetic alterations. Numerous studies show that targeting lncRNAs and molecules associated with the STAT۳ signaling pathway are promising therapeutic strategies for various cancers. This review highlighted the mechanisms of the upstream lncRNAs of the STAT۳ signaling pathway. 

Keywords:

STAT۳ Transcription Factor , Genetics , Oncogenes , Tumor Suppressor , MicroRNAs