Circular RNA circ‐Ttc3 protects HaCaT cells from hypoxic injury by downregulation of miR‐449a

Abstract

Background Pressure ulcer (PU) is a common complication of acute and long‐time hospitalization, especially in elderly patients. The incidence and prevalence of PU are swiftly fortifying. Currently, our purpose was to investigate the functional impacts of circ‐Ttc3 on PU. Methods HaCaT cells were pretreated under hypoxia condition. Cell counting kit 8 assay and flow cytometry were utilized to test HaCaT cell viability and apoptosis. Quantitative reverse transcription polymerase chain reaction was utilized to determine circ‐Ttc3 and miR‐449a expression. Western blot was performed to examine apoptosis‐associated proteins expression. Subsequently, the above‐described investigations were reperformed after miR‐449a upregulation. Results Hypoxia induced apoptosis and declined viability in HaCaT cells. Circ‐Ttc3 expression was enhanced after transfection with circ‐Ttc3 expressing vector. Overexpressing circ‐Ttc3 raised viability and reduced apoptosis in HaCaT cells. Moreover, miR‐449a expression was elevated by hypoxia and reversed by overexpressing circ‐Ttc3. And circ‐Ttc3 exerted its effect via downregulating miR‐449a. Finally, overexpressing circ‐Ttc3 activated nuclear factor kappa‐B (NF‐κB) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathways via downregulating miR‐449a. Conclusion Our data suggested that circ‐Ttc3 alleviated hypoxic injury and activated NF‐κB and PI3K/AKT pathways by downregulating miR‐449a in HaCaT cells.

The progress and challenges of circRNA for diabetic foot ulcers: A mini-review

“…In addition, the increase of hypoxia conditions and the damage of cells' response to hypoxia are important reasons for the delay of wound healing (15). Yu et al (48) found that circ_Ttc3 alleviated hypoxic injury and activated NF-kB and PI3K/AKT signaling pathways by downregulating miR-449a in HEKs. Although a small amount of circRNAs has been found in wounds today, these targets provide us with great value in the treatment of chronic wounds or in the exploration of etiological mechanisms.…”

Role of microRNAs in Pressure Ulcer Immune Response, Pathogenesis, and Treatment

“…Two microRNAs, miR-449a and miR-135b, have been implicated in pressure injury pathophysiology utilizing in vitro models of hypoxia [83,84]. MiR-449a has largely been studied as a tumor suppressor with roles in inhibiting a variety of malignancies, including cervical cancer, prostate cancer, and osteosarcoma [104][105][106].…”

“…When miR-135b was inhibited, the effects of ligustrazine were lost, suggesting a direct role of miR-135b in the prevention of hypoxia-induced endothelial apoptosis. miR-135b was shown to increase the PI3K/AKT activity, the opposite effect of miR-449a, and acted to increase Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity, suggesting multiple pathways in decreasing hypoxia-induced endothelial apoptosis [84]. miR-135b has been shown to have similarly protective effects in myocardial ischemia-reperfusion injury [114].…”

“…miR-145 inhibits JNK and p38-MAPK signaling pathways, which are activated by ROS [87,121]. JNK has been shown to have a complex role in pressure ulcer pathophysiology, increasing ROS production but inhibiting apoptotic activity [84,87,121]. Increased levels of p38-MAPK have been shown to contribute to the ischemia-reperfusion injury seen in pressure ulcer pathogenesis, and miR-145 may downregulate this expression [23,25,87].…”