LIN28B enhances the chemosensitivity of colon cancer cells via inducing genomic instability by upsetting the balance between the production and removal of reactive oxygen species

被引：0

作者：

Wang, Tianzhen ^{[1
,2
]}

Weng, Mingjiao ^{[1
,2
,3
]}

Li, Kai ^{[1
,4
]}

Li, Guoli ^{[1
,5
]}

Hu, Shijie ^{[1
,2
]}

Hu, Ziyi ^{[1
,2
]}

Li, Yanping ^{[1
,2
]}

Li, Muhan ^{[1
,2
]}

Wu, Di ^{[6
]}

Yu, Fei ^{[7
]}

Liang, Zhigang ^{[3
]}

Wang, Guangyu ^{[8
]}

Li, Xiaobo ^{[1
,2
]}

机构：

[1] Heilongjiang Prov Key Lab Mol Oncol, 150 Haping Rd, Harbin 150081, Heilongjiang, Peoples R China

[2] Harbin Med Univ, Dept Pathol, 157 Baojian Rd, Harbin 150081, Heilongjiang, Peoples R China

[3] Shenzhen Second Peoples Hosp, Dept Stomatol, Shenzhen 518000, Peoples R China

[4] China Med Univ, Dept Oncol 2, Shengjing Hosp, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China

[5] Chifeng Municipal Hosp, Dept Anus & Intestine Surg, 1 Middle Sect Zhaowuda Rd, Chifeng 024000, Inner Mongolia, Peoples R China

[6] First Affiliated Hosp Harbin Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, 23 Youzheng St, Harbin 150001, Heilongjiang, Peoples R China

[7] China Med Univ, Dept Tradit Chinese Med, Shengjing Hosp, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China

[8] Harbin Med Univ, Canc Hosp, Dept Gastrointestinal Med Oncol, 150 Haping Rd, Harbin 150081, Heilongjiang, Peoples R China

来源：

CANCER LETTERS | 2025年 / 616卷

基金：

中国国家自然科学基金;

关键词：

LIN28B; Genomic instability; GSH; Inflammation; ROS; Colon cancer; DNA-DAMAGE; UP-REGULATION; TARGET; CHEMORESISTANCE; INFLAMMATION; PROGRESSION; EXPRESSION; HALLMARKS; APOPTOSIS; REVEALS;

D O I：

10.1016/j.canlet.2025.217572

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genomic instability is an enabling characteristic that allows cancer cells to acquire additional hallmarks of cancer through the accumulation of alterations in driver genes. Furthermore, it creates opportunities to enhance the sensitivity of cancer cells to chemotherapeutic agents targeting DNA, owing to the presence of incomplete DNA damage repair pathways. This study identifies LIN28B as a crucial regulator of colon cancer cells' sensitivity to DNA damage- or repair-related compounds by promoting genomic instability. LIN28B mechanistically reduces glutathione (GSH) synthesis and activity by inhibiting the expression of four GSH metabolic enzymes (GCLC, G6PD, GSTM4, and GSTT2B), thereby reducing the capacity of cells to eliminate reactive oxygen species (ROS). LIN28B enhances the proinflammatory signaling pathway in cancer cells through the upregulation of ARID3A, a transcription factor that transactivates PTGES and PTGES2, resulting in increased production of PGE2, a key inflammatory mediator that can elevate ROS generation. In conclusion, LIN28B altered the equilibrium of ROS production and elimination in colon cancer, resulting in elevated ROS levels and subsequent genomic instability.

引用

页数：12

共 49 条

[1]

Hanahan D., Weinberg R.A., The hallmarks of cancer, Cell, 100, 1, pp. 57-70, (2000)

[2]

Hanahan D., Weinberg R.A., Hallmarks of cancer: the next generation, Cell, 144, 5, pp. 646-674, (2011)

[3]

Xie J., Wen M., Zhang J., Wang Z., Wang M., Qiu Y., Et al., The roles of RNA helicases in DNA damage repair and tumorigenesis reveal precision therapeutic strategies, Cancer Res., 82, 5, pp. 872-884, (2022)

[4]

Wang T., Hao D., Yang S., Ma J., Yang W., Zhu Y., Et al., miR-211 facilitates platinum chemosensitivity by blocking the DNA damage response (DDR) in ovarian cancer, Cell Death Dis., 10, 7, (2019)

[5]

Huang J.W., Wang Y., Dhillon K.K., Calses P., Villegas E., Mitchell P.S., Et al., Systematic screen identifies miRNAs that target RAD51 and RAD51D to enhance chemosensitivity, Mol. Cancer Res., 11, 12, pp. 1564-1573, (2013)

[6]

Rasola C., Laurent-Puig P., Andre T., Falcoz A., Lepage C., Aparicio T., Et al., Time to recurrence and its relation to survival after recurrence in patients resected for stage III colon cancer, European journal of cancer (Oxford, England : 1990), 194, (2023)

[7]

Amatu A., Mauri G., Tosi F., Bencardino K., Bonazzina E., Gori V., Et al., Efficacy of retreatment with oxaliplatin-based regimens in metastatic colorectal cancer patients: the RETROX-CRC retrospective study, Cancers, 14, 5, (2022)

[8]

Yang Y., Wei Q., Tang Y., Yuanyuan W., Luo Q., Zhao H., Et al., Loss of hnRNPA2B1 inhibits malignant capability and promotes apoptosis via down-regulating Lin28B expression in ovarian cancer, Cancer Lett., 475, pp. 43-52, (2020)

[9]

King C.E., Cuatrecasas M., Castells A., Sepulveda A.R., Lee J.S., Rustgi A.K., LIN28B promotes colon cancer progression and metastasis, Cancer Res., 71, 12, pp. 4260-4268, (2011)

[10]

Chen C., Bai L., Cao F., Wang S., He H., Song M., Et al., Targeting LIN28B reprograms tumor glucose metabolism and acidic microenvironment to suppress cancer stemness and metastasis, Oncogene, 38, 23, pp. 4527-4539, (2019)

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