环状非编码RNA 3-羟基-3-甲基戊二酰辅酶A合酶1影响胰腺癌细胞增殖和糖酵解

CAO  Zhen-zhen1; XU  Kun2; GUO  Er-tao1; YAN  Chun-hao1; YANG  Wen-yi1*

doi:10.16098/j.issn.0529-1356.2026.04.007

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解剖学报 ›› 2026, Vol. 57 ›› Issue (4) : 444-451. DOI: 10.16098/j.issn.0529-1356.2026.04.007

肿瘤生物学

环状非编码RNA 3-羟基-3-甲基戊二酰辅酶A合酶1影响胰腺癌细胞增殖和糖酵解

曹振振¹徐坤²郭二涛¹闫春豪¹杨文义^1*

作者信息 +

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*

Author information +

文章历史 +

摘要

目的探讨环状非编码RNA 3-羟基-3-甲基戊二酰辅酶A合酶1（circHMGCS1）调控微RNA-335-5p（miR-335-5p）/肌球蛋白重链9（MYH9）通路影响胰腺癌细胞增殖和糖酵解的作用及机制。方法 HE染色检测胰腺癌组织形态；Real-time PCR检测17例胰腺癌患者胰腺癌组织及胰腺癌细胞PANC-1、Pan02和BXPC-3 中circHMGCS1、miR-335-5p及MYH9 mRNA表达。PANC-1细胞分为胰腺癌组、敲低对照组、circHMGCS1敲低组、上调对照组、miR-335-5p上调组、circHMGCS1敲低+anti-miR-阴性对照（NC）组、circHMGCS1敲低+anti-miR-335-5p组，集落形成实验和CCK-8法检测细胞增殖；相关试剂盒检测细胞上清液中葡萄糖摄取量、乳酸产生量；Western blotting检测细胞MYH9、增殖细胞核抗原（PCNA）、己糖激酶2（HK2）、丙酮酸激酶M2型（PKM2）蛋白表达；circHMGCS1与miR-335-5p/MYH9的关系验证。结果癌旁组织结构正常，而胰腺癌组织呈现正常腺泡结构丧失、细胞核深染及多形性等恶性特征。胰腺癌组织circHMGCS1及MYH9 mRNA表达显著高于癌旁组织，miR-335-5p表达显著低于癌旁组织（P<0.05）；PANC-1、Pan02和BXPC-3细胞中circHMGCS1及MYH9 mRNA表达显著高于H6C7细胞，miR-335-5p表达显著低于H6C7细胞，且PANC-1细胞变化趋势最明显（P<0.05）。敲低circHMGCS1或上调miR-335-5p后，MYH9 mRNA表达、集落形成率、450 nm吸光度（A450）值、葡萄糖摄取量、乳酸产生量及MYH9、PCNA、HK2、PKM2蛋白降低，miR-335-5p表达升高（P<0.05）；Anti-miR-335-5p逆转了敲低circHMGCS1对PANC-1细胞糖酵解及增殖的抑制作用。CircHMGCS1靶向调控miR-335-5p/MYH9。结论 CircHMGCS1可能通过调控miR-335-5p/MYH9通路抑制PANC-1细胞糖酵解进而抑制细胞增殖。

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.

导出引用

曹振振徐坤郭二涛闫春豪杨文义. 环状非编码RNA 3-羟基-3-甲基戊二酰辅酶A合酶1影响胰腺癌细胞增殖和糖酵解[J]. 解剖学报. 2026, 57(4): 444-451 https://doi.org/10.16098/j.issn.0529-1356.2026.04.007

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

中图分类号： R363 R735.9

参考文献

[1] Zhang J, Sun W, Wu W, et al. METTL3-dependent m6A methylation of circCEACAM5 fuels pancreatic cancer progression through DKC1 activation [J]. Cell Mol Life Sci, 2025, 82(1): 132-146.

[2] Mao Y, Su X, Guo Q, et al. Long non-coding RNA LINC00930 targeting miR-6792-3p/ZBTB16 regulates the proliferation and EMT of pancreatic cancer [J]. BMC Cancer, 2024, 24(1): 638-651.

[3] Wang Y, Hu J, Chen C, et al. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc [J]. Open Life Sci, 2024, 19(1): 20220813.

[4] Li F, Si W, Xia L, et al. Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma [J]. Mol Cancer, 2024, 23(1): 90-113.

[5] Ge W, Wang Y, Quan M, et al. Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib [J]. Mol Cancer, 2024, 23(1): 48-65.

[6] He J, Zhao H, Liu X, et al. Sevoflurane suppresses cell viability and invasion and promotes cell apoptosis in colon cancer by modulating exosome-mediated circ-HMGCS1 via the miR-34a-5p/SGPP1 axis [J]. Oncol Rep, 2020, 44(6): 2429-2442.

[7] Wang J, He Z, Xu J, et al. Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling [J]. Cell Death Dis, 2021, 12(1): 36-50.

[8] Meng L, Zhang Y, Wu P, et al. CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 [J]. Mol Cancer, 2022, 21(1): 121-143.

[9] Notoya G, Kishikawa T, Yasugi K, et al. WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway [J]. J Gastroenterol, 2025, 60(3): 370-384.

[10] Zhu Y, Liang L, Zhao Y, et al. CircNUP50 is a novel therapeutic target that promotes cisplatin resistance in ovarian cancer by modulating p53 ubiquitination [J]. J Nanobiotechnology, 2024, 22(1): 35-51.

[11] Fang Z, Wu Z, Yu C, et al. EIF4E-mediated biogenesis of circPHF14 promotes the growth and metastasis of pancreatic ductal adenocarcinoma via Wnt/β-catenin pathway [J]. Mol Cancer, 2025, 24(1): 56-75.

[12] Wu X, Zhou S, Wang L, et al. Circ_103809 aggravates the malignant phenotype of pancreatic cancer through modulating miR-197-3p/TSPAN3 axis [J]. Mol Biotechnol, 2024, 66(9): 2455-2466.

[13] Liang H, Zhan J, Chen Y, et al. Tryptophan deficiency induced by indoleamine 2,3-dioxygenase 1 results in glucose transporter 1-dependent promotion of aerobic glycolysis in pancreatic cancer [J]. MedComm (2020), 2024, 5(5): e555.

[14] Sun BW, Cheng Y. Research progress on the role and regulatory mechanism of fructose-1,6-bisphosphatase 1 in tumorigenesis and development [J]. Acta Anatomica Sinica, 2025, 56(2): 248-251. (in chinese)

孙伯文, 程媛. 果糖-1,6-二磷酸酶1在肿瘤发生发展中的作用及调控机制的研究进展 [J]. 解剖学报, 2025, 56(2): 248-251.

[15] Chen Y, Zhang F, Dai S, et al. Lactate-associated gene MCU promotes the proliferation, migration, and invasion of pancreatic ductal adenocarcinoma [J]. BMC Cancer, 2025, 25(1): 913-930.

[16] Zhao R, Yi Y, Liu H, et al. RHOF promotes Snail1 lactylation by enhancing PKM2-mediated glycolysis to induce pancreatic cancer cell endothelial-mesenchymal transition [J]. Cancer Metab, 2024, 12(1): 32-47.

[17] Li F, Liu JW, Lu ChF, et al. Mechanism of circHMGCS1/miR-335-5p/ITGB2 in regulating the proliferation, migration and invasion of breast cancer MDA-MB-231 cells [J]. Chinese Journal of Diagnostic Pathology, 2023, 30(8): 739-743, 793. (in chinese)

李菲, 刘佳玮, 鲁程绯, 等. circHMGCS1/miR-335-5p/ITGB2调控乳腺癌MDA-MB-231细胞增殖、迁移、侵袭的机制研究 [J]. 诊断病理学杂志, 2023, 30(8): 739-743, 793.

[18] Fu Y, Chen B, Gao T, et al. CircSLC25A16 facilitates the development of non-small-cell lung cancer through the miR-335-5p/CISD2 axis [J]. Thorac Cancer, 2024, 15(19): 1490-1501.

[19] Cao J, Zhang Y, Yang J, et al. NEAT1 regulates pancreatic cancer cell growth, invasion and migration though mircroRNA-335-5p/c-met axis [J]. Am J Cancer Res, 2016, 6(10): 2361-2374.

[20] Li Y, Wang L, Zhang N, et al. CircKCNQ5 controls proliferation, migration, invasion, apoptosis, and glycolysis of multiple myeloma cells by modulating miR-335-5p/BRD4 axis [J]. Histol Histopathol, 2023, 38(5): 525-536.

[21] Cao X, Meng X, Fu P, et al. circATP2A2 promotes osteosarcoma progression by upregulating MYH9 [J]. Open Med (Wars), 2021, 16(1): 1749-1761.