Exploring the mechanism of occupational cadmium exposure inducing malignant biological behavior of colorectal cancer cells based on the circ-0072309/miR-26a-5p pathway

Abstract

Abstract:

Objective To explore the mechanism of occupational cadmium exposure-induced malignant biological behavior of colorectal cancer cells based on the circular RNA-0072309（circ-0072309）/microRNA-26a-5p（miR-26a-5p） pathway. Methods From February to May 2024，experiments were conducted at Baoding First Central Hospital. Colorectal cancer cells were divided into SW480 group，50 nmol/L CdCl₂ group，100 nmol/L CdCl₂ group，and 200 nmol/L CdCl₂ group. The cells were cultured for 72 hours. After the experiment，cell proliferation，monoclonal number，and apoptosis level，invasion and migration level，epithelial mesenchymal transition（EMT） level were measured. Circ-0072309，miR-26a-5p，and phosphatase and tensin homolog deleted on chromosome 10（PTEN） levels were detected by RT-PCR and West-blot. Results Compared with the colorectal cancer cell SW480 group，Vimentin levels，number of single cell clones，migration distance，miR-26a-5p mRNA levels（0.97±0.16 vs 1.63±0.27，2.48±0.41，3.35±0.59），the survival rate，and number of membrane penetration of the 50，100，and 200 nmol/L CdCl₂ groups increased，while PTEN mRNA protein levels（3.24±0.54 vs 2.63±0.43，1.89±0.32，1.01±0.16；1.28±0.21 vs 0.95±0.16，0.60±0.10，0.23±0.05），epithelial cadherin（E-cadherin），circ-0072309 mRNA（3.59±0.61 vs 2.89±0.48，2.12±0.35，1.35±0.23），and apoptosis rate decreased，and the differences were statistically significant（all P<0.05）. Moreover，with the increase of CdCl₂ exposure dose，Vimentin levels，number of single cell clones，migration distance，miR-26a-5p mRNA level，survival rate，and number of membrane penetration of the 50，100，and 200 nmol/L CdCl₂ groups showed an upward trend，while PTEN mRNA protein levels，E-cadherin level，circ-0072309 mRNA，and apoptosis rate showed a downward trend，and the differences were statistically significant（all P<0.05）. Conclusion Occupational Cd exposure inhibits the expression of circ-0072309 and releases its adsorption to miR-26a-5p，leading to overexpression of miR-26a-5p and targeted down regulation of PTEN gene，activating PI3K/AKT pathway，thereby promoting the proliferation，invasion and migration of colorectal cancer cells and EMT process（Vimentin↑/E-cadherin↓） in a dose-dependent manner（50-200 nmol/L），and inhibiting apoptosis. This study is the first to clarify the ceRNA regulatory mechanism of circ-0072309/miR-26a-5p/PTEN axis in cadmium carcinogenesis，providing a theoretical basis for molecular intervention of occupational cadmium exposure-related colorectal cancer and the development of circRNA biomarkers.

Key words: circ-0072309, miR-26a-5p, Occupational cadmium exposure, Colorectal cancer, Malignant biological behavior

CLC Number:

R735.3

XIN Qingwang, ZHANG Peijun. Exploring the mechanism of occupational cadmium exposure inducing malignant biological behavior of colorectal cancer cells based on the circ-0072309/miR-26a-5p pathway. [J]OCCUPATION AND HEALTH, 2025, 41(24): 3350-3356.

Figures/Tables 11

References 19

[1]	DE ANGELIS C, GALDIERO G, MENAFRA D, et al. The environment and male reproductive system:The potential role and underlying mechanisms of cadmium in testis cancer[J]. Crit Rev Toxicol, 2023, 53(7):412-435. DOI URL
[2]	CIROVIC A, SATARUG S. Toxicity tolerance in the carcinogenesis of environmental cadmium[J]. Int J Mol Sci, 2024, 25(3):1851-1854. DOI URL
[3]	TAVAKOLI A, EBRAHIMI P, NIKNEZHAD S, et al. Toxic mechanisms of cadmium and exposure as a risk factor for oral and gastrointestinal carcinomas[J]. Hum Exp Toxicol, 2023, 42(5):262-265.
[4]	CONN V M, CHINNAIYAN A M, CONN S J. Circular RNA in cancer[J]. Nat Rev Cancer, 2024, 15(6):1-17. DOI
[5]	ZHAO Y, LI J, XU L, et al. The decreased circular RNA hsa_circ_0072309 promotes cell apoptosis of ischemic stroke by sponging miR-100[J]. Eur Rev Med Pharmacol Sci, 2020, 24(8):65-67.
[6]	PANG W, HUANG F, ZHANG X, et al. Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p[J]. Biosci Rep, 2020, 40(5):237-239.
[7]	TAN H W, SEEN D L T, XU Y M, et al. Cadmium,cellular senescence,and cancer[J]. Rev Environ Contam Toxicol, 2023, 261(1):21-25.
[8]	KANWAL N, AL SAMARRAI O R, AL-ZAIDI H M H, et al. Comprehensive analysis of microRNA(miRNA) in cancer cells[J]. Cell Mol Biomed Rep, 2023, 3(2):89-97. DOI URL
[9]	REN G, YANG E J, TAO S, et al. MDM2 inhibition is synthetic lethal with PTEN loss in colorectal cancer cells via the p53-dependent mechanism[J]. Int J Biol Sci, 2023, 19(11):44-46.
[10]	ZHANG J, ZHANG Y, LIN X, et al. The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation[J]. Transl Cancer Res, 2023, 12(7):1863-1866. DOI URL
[11]	TARHONSKA K, JANASIK B, ROSZAK J, et al. Environmental exposure to cadmium in breast cancer-association with the Warburg effect and sensitivity to tamoxifen[J]. Biomed Pharmacother, 2023, 161(15):114435-114436. DOI URL
[12]	GUO X, QIN M, HONG H, et al. Circular RNA hsa_circ_0072309 inhibits the proliferation,invasion and migration of gastric cancer cells via inhibition of PI3K/AKT signaling by activating PPARγ/PTEN signaling[J]. Mol Med Rep, 2021, 23(5):1-8.
[13]	XU A, ZHU L, YAO C, et al. The therapeutic potential of circular RNA in triple-negative breast cancer[J]. Cancer Drug Resist, 2024, 56(7):521-524.
[14]	MAGALHÃES L, RIBEIRO-DOS-SANTOS A M, CRUZ R L, et al. Triple-negative breast cancer circRNAome reveals Hsa_circ_0072309 as a potential risk biomarker[J]. Cancers(Basel), 2022, 14(13):3280-3285.
[15]	CHEN T, SHAO S, LI W, et al. Retracted Article:The circular RNA hsa-circ-0072309 plays anti-tumour roles by sponging miR-100 through the deactivation of PI3K/AKT and mTOR pathways in the renal carcinoma cell lines[J]. Artif Cells Nanomed Biotechnol, 2019, 47(1):3638-3648. DOI PMID
[16]	MA X, DENG C. Circ_0044556 promotes the progression of colorectal cancer via the miR-665-dependent expression regulation of diaphanous homolog 1[J]. Dig Dis Sci, 2021, 24(11):1-13. DOI URL
[17]	CHEN R, MAO L, SHI R, et al. circRNA MYLK accelerates cervical cancer via up-regulation of RHEB and activation of mTOR signaling[J]. Cancer Manag Res, 2020, 9(5):3611-3621.
[18]	LI Y, FENG W, KONG M, et al. Exosomal circRNAs:A new star in cancer[J]. Life Sci, 2021, 269(15):119039-119042. DOI URL
[19]	YUAN F, SUN Q, XU Y, et al. Hsa_circ_0072309 inhibits proliferation and invasion of glioblastoma[J]. Pathol Res Pract, 2021, 222(14):153433-153436. DOI URL

组别	存活率（%）	单细胞克隆形成数目（个）	凋亡率（%）
200 nmol/L CdCl₂组	93.20±6.34^abc	155.35±15.1^abc	1.90±0.09^abc
100 nmol/L CdCl₂组	84.38±5.89^ab	98.25±10.25^ab	3.60±0.19^ab
50 nmol/L CdCl₂组	73.45±5.38^a	79.29±8.88^a	16.90±0.56^a
结直肠癌细胞SW480组	61.83±4.39	53.83±6.32	18.00±0.78
F值	109.415	165.216	189.554
P	<0.01	<0.01	<0.01

组别	存活率（%）	单细胞克隆形成数目（个）	凋亡率（%）
200 nmol/L CdCl₂组	93.20±6.34^abc	155.35±15.1^abc	1.90±0.09^abc
100 nmol/L CdCl₂组	84.38±5.89^ab	98.25±10.25^ab	3.60±0.19^ab
50 nmol/L CdCl₂组	73.45±5.38^a	79.29±8.88^a	16.90±0.56^a
结直肠癌细胞SW480组	61.83±4.39	53.83±6.32	18.00±0.78
F值	109.415	165.216	189.554
P	<0.01	<0.01	<0.01

组别	穿膜数（个）	迁移距离（μm）
200 nmol/L CdCl₂组	1852.63±302.52^abc	152.66±23.84^abc
100 nmol/L CdCl₂组	1025.58±159.96^ab	89.96±12.59^ab
50 nmol/L CdCl₂组	859.96±142.59^a	43.55±7.36^a
结直肠癌细胞SW480组	259.96±42.59	23.69±3.98
F值	398.654	254.239
P	<0.01	<0.01

组别	穿膜数（个）	迁移距离（μm）
200 nmol/L CdCl₂组	1852.63±302.52^abc	152.66±23.84^abc
100 nmol/L CdCl₂组	1025.58±159.96^ab	89.96±12.59^ab
50 nmol/L CdCl₂组	859.96±142.59^a	43.55±7.36^a
结直肠癌细胞SW480组	259.96±42.59	23.69±3.98
F值	398.654	254.239
P	<0.01	<0.01

组别	E-cadherin蛋白（μmol/L）	Vimentin蛋白（μmol/L）
200 nmol/L CdCl₂组	105.69±15.59^abc	505.25±94.69^abc
100 nmol/L CdCl₂组	217.69±35.22^ab	386.69±65.69^ab
50 nmol/L CdCl₂组	345.14±58.52^a	255.63±42.29^a
结直肠癌细胞SW480组	459.65±75.25	159.96±25.69
F值	156.324	204.329
P	<0.01	<0.01