Circular non-coding RNA 3-hydroxy-3-methylglutaryl-CoA synthase 1 affecting the proliferation and glycolysis of pancreatic cancer cells

曹振振1徐坤2郭二涛1闫春豪1杨文义1*

doi:10.16098/j.issn.0529-1356.2026.04.007

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (4) : 444-451. DOI: 10.16098/j.issn.0529-1356.2026.04.007

Circular non-coding RNA 3-hydroxy-3-methylglutaryl-CoA synthase 1 affecting the proliferation and glycolysis of pancreatic cancer cells

CAO Zhen-zhen¹, XU Kun², GUO Er-tao¹, YAN Chun-hao¹, YANG Wen-yi^1*

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Abstract

Objective To investigate the effect and mechanism of circular RNA 3-hydroxy-3-methylglutaryl-CoA synthase 1 (circHMGCS1) regulating pancreatic cancer cell proliferation and glycolysis via the microRNA-335-5p（miR-335-5p）/myosin heavy chain 9 (MYH9) pathway. Methods HE staining detected pancreatic cancer tissue morphology; Real-time PCR was used to measure the expression of circHMGCS1, miR-335-5p, and MYH9 mRNA in 17 cases of pancreatic cancer tissue and pancreatic cancer cell lines (PANC-1, Pan02, BXPC-3). PANC-1 cells were divided into: pancreatic cancer group, knockdown control group, circHMGCS1 knockdown group, upregulation control group, miR-335-5p-upregulated group, circHMGCS1-silenced + anti-miR-negative control (NC) group, and circHMGCS1-silenced + anti-miR-335-5p group. Cell proliferation was assessed using colony formation and CCK-8 assays. Glucose uptake and lactate production in the cell supernatant were measured using related kits. Western blotting was performed to detect MYH9, proliferating cell nuclear antigen (PCNA), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2) protein levels. The regulatory relationship between circHMGCS1 and miR-335-5p/MYH9 was validated. Results Paracancerous tissue showed normal structure, while pancreatic cancer tissue exhibited malignant features such as loss of normal acinar structure, hyperchromatic nuclei, and nuclear pleomorphism. CircHMGCS1 and MYH9 mRNA expression were significantly higher in pancreatic cancer tissues than in adjacent normal tissues, while miR-335-5p expression was significantly lower (P<0.05). In PANC-1, Pan02, and BXPC-3 cells, circHMGCS1 and MYH9 mRNA expression were significantly higher than in H6C7 cells, whereas miR-335-5p expression was significantly lower, with the most pronounced changes observed in PANC-1 cells (P<0.05). After knockdown circHMGCS1 or upregulating miR-335-5p, the expression of MYH9 mRNA, clone formation rate, 450 nm absorbance（A450）value, glucose uptake, lactate production, as well as the protein levels of MYH9, PCNA, HK2, and PKM2 decreased, while the expression of miR-335-5p increased (P<0.05); Anti-miR-335-5p reversed the inhibitory effect of circHMGCS1 knockdown on glycolysis and proliferation of PANC-1 cells. circHMGCS1 targets and regulates miR-335-5p/MYH9. Conclusion CircHMGCS1 may inhibit glycolysis in PANC-1 cells by regulating the miR-335-5p/MYH9 axis, thereby suppressing cell proliferation.

Key words

Circular non\

/ coding RNA 3-hydroxy-3-methylglutaryl-CoA synthase 1 / MicroRNA-335-5p / Myosin heavy chain 9 / Pancreatic cancer / Glycolysis / Western blotting；Human

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CAO Zhen-zhen , XU Kun , GUO Er-tao , YAN Chun-hao , YANG Wen-yi.

Circular non-coding RNA 3-hydroxy-3-methylglutaryl-CoA synthase 1 affecting the proliferation and glycolysis of pancreatic cancer cells

[J]. Acta Anatomica Sinica. 2026, 57(4): 444-451 https://doi.org/10.16098/j.issn.0529-1356.2026.04.007

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