circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR‐92a‐2‐5p/KLLN Pathway

Abstract

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L–miR-92a-2-5p–KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p–KLLN pathway. Thus, targeting the novel circAMOTL1L–miR-92a-2-5p–KLLN regulatory axis might provide a therapeutic strategy for RCC.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma

“…Among these, 54 studies were excluded due to the following reasons: non-original articles (n = 19), conference abstracts (n = 3), and studies without available data for any of the defined outcomes (n = 32). Ultimately, 41 studies consisting of 3485 patients with RCC were included in this study, among which 26 studies investigated clinicopathological features, 34,37-39,42-4 4,46-6 4 31 studies evaluated prognostic outcomes, 23,25,[34][35][36][37][38][39][40][41][42][43][44]46,48,50,51,[53][54][55][56][57][63][64][65][66][67][68][69][70][71] and eight studies assessed the diagnosis of RCC. 34,[40][41][42]48,58,72,73 The studies were published between 2017 and 2022 and were conducted in China (n = 38), Germany (n = 2), and Canada (n = 1).…”

“…Among 26 studies with a total of 2048 patients, the expression of six circRNAs (circ-0001451, circ-RAPGEF5, circ-AMOTL1L, circ-ESRP1, circ-CYP24A1, and circ-DVL1) was downregulated, 34,43,57,58,62,63 whereas 18 circRNAs (circ-001895, circ-001287, circ-HIPK3, circ-PDK1, circ-MYLK, circ-0085576, circ-PTCH1, circ-400,068, circ-NUP98, circ-001842, circ-RS-7 (two studies), circ-AKT1, circ-SDHC (two studies), circ-TLK1, circ-SNX6, circ-0054537, circ-CHST15, and circ-PPP6R3) were upregulated in the RCC tissue [37][38][39]42,44,[46][47][48][49][50][51][52][53][54][55][56][59][60][61]64 (Table S1). The tumor suppressor (downregulated) circRNAs were associated with smaller tumor size (OR = 0.71 [95% CI 0.58-0.87]; p = 0.001), lower T stage (OR = 0.45 [95% CI 0.27-0.75]; p = 0.002), less lymph node metastasis (OR = 0.29 [95% CI 0.12-0.72]; p = 0.008), less distant metastasis (OR = 0.24 [95% CI 0.14-0.41]; p < 0.001), and lower TNM stage (OR = 0.36 [95% CI 0.24-0.56]; p < 0.001).…”

“…In total, 31 studies, including 2906 patients, investigated the prognostic endpoints (two studies reported the results for three circR-NAs, 40,41 and each of the remaining 29 studies examined only one circRNA 23,25,[34][35][36][37]39,[42][43][44]46,48,50,51,[53][54][55][56][57]63,[65][66][67][68][69][70][71] ). These studies evaluated 30 distinct circRNAs (three circRNAs were investigated in more than one study: 1.…”

miR-92a-2-5p Regulates the Proliferation and Differentiation of ASD-Derived Neural Progenitor Cells

“…Previously, cancer-related studies have shown that miR-92a can suppress cell proliferation and induce apoptosis [ 35 , 36 ]. Consistent with these findings, upregulation of miR-92a-2-5p could inhibit proliferation and enhance apoptosis of intestinal cells, indicating that miR-92a-2-5p may play an important role in the cell cycle, as well as in growth and differentiation [ 20 ].…”

circRNAs May Be Involved in Dysfunction of Neutrophils of Type 2 Diabetic Mice through Regulation of Specific miRNAs

“…In contrast, miR-92a-2-5p showed significant expression changes in diabetic-derived neutrophils. miR-92a-2-5p was reported to induce apoptosis by post-transcriptional repression of miR-92a-2-5p through regulation of circAMOTL1L in renal cell carcinoma [ 41 ]. Diabetic wounds in type 2 diabetic mice have myeloid cell accumulation in the wound area, and these cells cause abnormal apoptosis.…”