FOXO3-Activated HOTTIP Sequesters miR-615-3p away from COL2A1 to Mitigate Intervertebral Disc Degeneration

Research progress on long non‑coding RNAs in non‑infectious spinal diseases (Review)

“…After downregulation, angiopoietin 2 has been shown to be inhibited in a miR-17-3p-dependent manner, promoting ECM remodelling, inhibiting NP cell apoptosis and improving IDD ( 68 ). A recent study showed that the transcription factor FOXO3 may enhance the competitive binding of HOXA transcript at the distal tip (HOTTIP) and miR-615-3p by activating HOTTIP transcription, increasing the expression of the target gene collagen type II α1 of miR-615-3p, inducing NP cell proliferation, and reducing apoptosis to prevent ECM degradation ( 69 ). Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1), like HOTTIP, was also shown to be expressed at low levels in degenerative NP tissues.…”

“…As aforementioned, PART1 not only affects the synthesis and degradation of the ECM through the miR-93/matrix metalloproteinase-2 signalling axis, but increased PART1 expression in degenerated tissues can also promote the apoptosis of NP cells and promote IDD ( 67 ). Similarly, HOTTIP, while preventing ECM degradation through a ceRNA mechanism, can also inhibit the apoptosis of NP cells and promote proliferation, improving the progression of IDD ( 69 ). In degenerated NP cells, small nucleolar RNA host gene 6 (SNHG6) expression has been reported to be upregulated and SNHG6 can induce NP cell apoptosis by targeting miR-101-3p ( 77 ).…”