Ding Han-Xi, Wu Ye-Feng, Xu Qian, Yuan Yuan
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, China.
Key Laboratory of Cancer Etiology and Prevention in Liaoning Provincial Education Department, the First Hospital of China Medical University, Shenyang 110001, China.
J Cancer. 2021 May 27;12(14):4389-4398. doi: 10.7150/jca.47787. eCollection 2021.
Pepsinogen C (PGC) is considered to be the final product of mature differentiated gastric mucosa. The expression level of PGC in gastric mucosa is clearly decreased upon the development of gastric cancer (GC). However, the mechanism behind PGC's down-regulation remains unclear and needs to be clarified. This study aimed to identify PGC-related ncRNAs with the potential to be PGC post-transcriptional regulators and to further explore the association between these ncRNAs and the clinicopathological parameters of GC. Bioinformatic software was used to predict miRNAs binding specifically to PGC and circRNAs binding specifically to these candidate miRNAs. Dual-luciferase reporter assay was performed to validate the completely complementary pairing of PGC and PGC-related ncRNAs. qRT-PCR was applied to determine the expression levels of PGC and PGC-related ncRNAs in GC tissue. hsa-let-7c was predicted to bind to the PGC gene, which was confirmed by dual-luciferase reporter assay. hsa_circ_0001483 and hsa_circ_0001324 were identified to bind to hsa-let-7c by bioinformatic analysis and dual-luciferase reporter assay. In addition, the hsa_circ_0001483/hsa_circ_0001324 -hsa-let-7c-PGC axis was confirmed in tissue by qRT-PCR. The expression level of hsa_circ_0001483 was correlated with peritumoral inflammatory cell infiltration and lymphatic metastasis. hsa_circ_0001483, hsa_circ_0001324, and let-7c were newly identified and validated as PGC-related ncRNAs and showed associations with the clinicopathological features of GC. The hsa_circ_0001483/hsa_circ_0001324-hsa-let-7c-PGC axis in GC may account for the down-regulation of PGC in GC tissue.
胃蛋白酶原C（PGC）被认为是成熟分化胃黏膜的终产物。在胃癌（GC）发生发展过程中，胃黏膜中PGC的表达水平明显降低。然而，PGC下调背后的机制仍不清楚，有待阐明。本研究旨在鉴定具有成为PGC转录后调节因子潜力的PGC相关非编码RNA，并进一步探讨这些非编码RNA与GC临床病理参数之间的关联。使用生物信息学软件预测与PGC特异性结合的miRNA以及与这些候选miRNA特异性结合的环状RNA。进行双荧光素酶报告基因检测以验证PGC与PGC相关非编码RNA的完全互补配对。应用qRT-PCR测定GC组织中PGC和PGC相关非编码RNA的表达水平。预测hsa-let-7c与PGC基因结合，双荧光素酶报告基因检测证实了这一点。通过生物信息学分析和双荧光素酶报告基因检测鉴定出hsa_circ_0001483和hsa_circ_0001324与hsa-let-7c结合。此外，通过qRT-PCR在组织中证实了hsa_circ_0001483/hsa_circ_0001324 -hsa-let-7c-PGC轴。hsa_circ_0001483的表达水平与肿瘤周围炎性细胞浸润和淋巴转移相关。hsa_circ_0001483、hsa_circ_0001324和let-7c是新鉴定并验证的与PGC相关的非编码RNA，且与GC的临床病理特征相关。GC中的hsa_circ_0001483/hsa_circ_0001324-hsa-let-7c-PGC轴可能解释了GC组织中PGC的下调。
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