Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives

Abstract

Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncRNAs, or their crosstalk play complicated roles in the initiation, metastasis, apoptosis and drug resistance of cancer, allowing ncRNAs related to the Hh pathway to serve as clinical biomarkers for targeted cancer therapy. In this review, we attempt to depict the multiple patterns of ncRNAs in the progression of malignant tumors via interactions with the Hh crucial elements in order to better understand the complex regulatory mechanism, and focus on Hh associated ncRNA therapeutics aimed at boosting their application in the clinical setting.

Resveratrol Induces Apoptosis, Suppresses Migration, and Invasion of Cervical Cancer Cells by Inhibiting the Hedgehog Signaling Pathway

“…The results of qPCR and western blotting had showed that PUR could upregulate the Shh, SMO, and Gli1 expression, which suggested that PUR indeed activated the Hedgehog signaling pathway. Many studies had shown that activation of the Hedgehog signaling pathway could accelerate the progression of various tumors, and blocking this pathway was a new strategy for the treatment of tumors [38][39][40][41]. PUR-induced activation of Hedgehog signaling pathway could not promote the malignant characteristics of cervical cancer cells in our studies, which seemed to contradict previous researches.…”

LncRNA MIR31HG fosters stemness malignant features of non-small cell lung cancer via H3K4me1- and H3K27Ace-mediated GLI2 expression

“…Previous studies, including the present study, have demonstrated the essential role of the Hedgehog cascade, particularly its executor GLI1, in cancer stem cell-mediated NSCLC development and progression [16][17][18]. The Hedgehog cascade can be stimulated in a canonical way, dependent on the translocation of its upstream regulator SMO, or in an uncanonical way, dependent on the expression of aberrant non-coding RNAs [19,20]. lncRNAs function at the epigenetic, transcription, and posttranscription levels in either a transor cis-manner [21].…”

Emerging role of non-coding RNAs in the regulation of Sonic Hedgehog signaling pathway

“…It is estimated that one-third of malignancies are correlated with abnormal activity of the Hh signaling pathway [ 70 ]. Dysregulation of Hh signaling can contribute to the imitation, growth, metastasis, and apoptosis of several types of cancers.…”

“…In fact, three patterns of induction of the Hh signaling cascade have been identified in several cancers. These patterns are ligand independent oncogenic Hh pathway, autocrine or juxtacrine and paracrine or reverse paracrine patterns [ 70 ].…”