LITAF Inhibits Colorectal Cancer Stemness and Metastatic Behavior by Regulating FOXO1-mediated SIRT1 Expression

Overview

Journal Clin Exp Metastasis

Specialty Oncology

Date 2023 Jun 2

PMID 37266842

Authors

Jiao Guan

Zheng-Yun Zhang

Jian-Hua Sun

Xin-Ping Wang

Zun-Qiang Zhou

Lei Qin

Affiliations

Soon will be listed here.

Abstract

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) is a transcription factor that activates the transcription of TNF-α and regulates the inflammatory response. LITAF has been found to have potential anti-cancer effects of in several tumors. However, the role of LITAF in colorectal cancer (CRC) remains unclear. Through a comprehensive pan-cancer analysis of the Cancer Genome Atlas (TCGA), LITAF was identified as a differentially downregulated gene in CRC. We hypothesized that LITAF may participate in the modulation of CRC progression. The present study was aimed to investigate the expression profile of LITAF in CRC and its effect on metastatic behavior and stemness as well as the underlying molecular mechanism. The expression profile of LITAF in CRC, and its relationship with the prognosis of CRC were explored using public databases. LITAF expression was detected by quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. Furthermore, the effects of overexpression or knockdown of LITAF on cell proliferation, apoptosis, migration, invasion, and stemness of CRC cells were investigated in vitro. The regulatory effect of LITAF on forkhead Box O 1 (FOXO1)-sirtuin 1 (SIRT1) signaling axis was also explored. In addition, a xenograft mouse model was used to investigate the in-vivo role of LITAF. LITAF was downregulated in tumor tissues and its expression was associated with the prognosis, pathological stage and liver metastasis. In-vitro experiments confirmed that LITAF inhibited tumor cell proliferation, migration, invasion and stemness, and induced cell apoptosis. In vivo experiments demonstrated that LITAF inhibited the tumorigenicity and liver metastasis in tumor-bearing mice. Additionally, LITAF promoted FOXO1-mediated SIRT1 inhibition, thus regulating cancer stemness and malignant phenotypes. LITAF was silenced in CRC and it participated in the progression of CRC by inhibiting CRC cell stemness, and malignant phenotypes. Therefore, LITAF may serve as a novel biomarker of CRC prognosis.

Citing Articles

The role of SIRT1 in autophagy and drug resistance: unveiling new targets and potential biomarkers in cancer therapy.

Tang Y, Ju W, Liu Y, Deng Q Front Pharmacol. 2024; 15:1469830.

PMID: 39403142 PMC: 11471651. DOI: 10.3389/fphar.2024.1469830.

Bulk and single-cell RNA sequencing analyses coupled with multiple machine learning to develop a glycosyltransferase associated signature in colorectal cancer.

Chen X, Zhang D, Ou H, Su J, Wang Y, Zhou F Transl Oncol. 2024; 49:102093.

PMID: 39217850 PMC: 11402624. DOI: 10.1016/j.tranon.2024.102093.

LINC00173 silence and estrone supply suppress ER breast cancer by estrogen receptor α degradation and LITAF activation.

Xie Y, Shan M, Yu J, Du Y, Wu C, Liu S Cancer Sci. 2024; 115(7):2318-2332.

PMID: 38705575 PMC: 11247560. DOI: 10.1111/cas.16201.

LITAF Promotes Atherosclerotic Plaque Formation by Stimulating the NF-κB Inflammatory Pathway.

Li W, Zhou W, Li X, Jiang X, Deng Y, Shen J Curr Med Sci. 2023; 43(6):1201-1205.

PMID: 37848750 DOI: 10.1007/s11596-023-2802-x.

References

Dekker E, Tanis P, Vleugels J, Kasi P, Wallace M . Colorectal cancer. Lancet. 2019; 394(10207):1467-1480. DOI: 10.1016/S0140-6736(19)32319-0. View

Dariya B, Aliya S, Merchant N, Alam A, Nagaraju G . Colorectal Cancer Biology, Diagnosis, and Therapeutic Approaches. Crit Rev Oncog. 2021; 25(2):71-94. DOI: 10.1615/CritRevOncog.2020035067. View

Wang J, Cai H, Liu Q, Xia Y, Xing L, Zuo Q . Cinobufacini Inhibits Colon Cancer Invasion and Metastasis via Suppressing Wnt/β-Catenin Signaling Pathway and EMT. Am J Chin Med. 2020; 48(3):703-718. DOI: 10.1142/S0192415X20500354. View

Fiorentino F, Mautone N, Menna M, DAcunzo F, Mai A, Rotili D . Sirtuin modulators: past, present, and future perspectives. Future Med Chem. 2022; 14(12):915-939. PMC: 9185222. DOI: 10.4155/fmc-2022-0031. View

Imai S, Guarente L . NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014; 24(8):464-71. PMC: 4112140. DOI: 10.1016/j.tcb.2014.04.002. View

Garcia-Peterson L, Li X . Trending topics of SIRT1 in tumorigenicity. Biochim Biophys Acta Gen Subj. 2021; 1865(9):129952. PMC: 8277705. DOI: 10.1016/j.bbagen.2021.129952. View

Zu G, Ji A, Zhou T, Che N . Clinicopathological significance of SIRT1 expression in colorectal cancer: A systematic review and meta analysis. Int J Surg. 2016; 26:32-7. DOI: 10.1016/j.ijsu.2016.01.002. View

Sun L, Zhi Z, Chen L, Zhou Q, Li X, Gan W . SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p. Cancer Lett. 2017; 409:104-115. DOI: 10.1016/j.canlet.2017.09.001. View

Fang H, Huang Y, Luo Y, Tang J, Yu M, Zhang Y . SIRT1 induces the accumulation of TAMs at colorectal cancer tumor sites via the CXCR4/CXCL12 axis. Cell Immunol. 2021; 371:104458. DOI: 10.1016/j.cellimm.2021.104458. View

10.

An Y, Wang B, Wang X, Dong G, Jia J, Yang Q . SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK/FOXO3 positive feedback loop. Cell Death Dis. 2020; 11(2):115. PMC: 7015918. DOI: 10.1038/s41419-020-2308-4. View

11.

Wang T, Chern E, Hsu C, Tseng K, Chao H . SIRT1-Mediated Expression of CD24 and Epigenetic Suppression of Novel Tumor Suppressor miR-1185-1 Increases Colorectal Cancer Stemness. Cancer Res. 2020; 80(23):5257-5269. DOI: 10.1158/0008-5472.CAN-19-3188. View

12.

Yao J, Yang J, Yang Z, Wang X, Yang T, Ji B . FBXW11 contributes to stem-cell-like features and liver metastasis through regulating HIC1-mediated SIRT1 transcription in colorectal cancer. Cell Death Dis. 2021; 12(10):930. PMC: 8511012. DOI: 10.1038/s41419-021-04185-7. View

13.

Yang S, Pang L, Dai W, Wu S, Ren T, Duan Y . Role of Forkhead Box O Proteins in Hepatocellular Carcinoma Biology and Progression (Review). Front Oncol. 2021; 11:667730. PMC: 8190381. DOI: 10.3389/fonc.2021.667730. View

14.

Liu Y, Ao X, Jia Y, Li X, Wang Y, Wang J . The FOXO family of transcription factors: key molecular players in gastric cancer. J Mol Med (Berl). 2022; 100(7):997-1015. DOI: 10.1007/s00109-022-02219-x. View

15.

Chen F, Guo L, Di J, Li M, Dong D, Pei D . Circular RNA ubiquitin-associated protein 2 enhances autophagy and promotes colorectal cancer progression and metastasis via miR-582-5p/FOXO1 signaling. J Genet Genomics. 2021; 48(12):1091-1103. DOI: 10.1016/j.jgg.2021.07.017. View

16.

Dai X, Xie Y, Dong M . Cancer-associated fibroblasts derived extracellular vesicles promote angiogenesis of colorectal adenocarcinoma cells through miR-135b-5p/FOXO1 axis. Cancer Biol Ther. 2022; 23(1):76-88. PMC: 8812748. DOI: 10.1080/15384047.2021.2017222. View

17.

Kim S, Ko Y, Park J, Choi Y, Park J, Kim Y . Forkhead Transcription Factor FOXO1 Inhibits Angiogenesis in Gastric Cancer in Relation to SIRT1. Cancer Res Treat. 2015; 48(1):345-54. PMC: 4720104. DOI: 10.4143/crt.2014.247. View

18.

Liu H, Liu N, Zhao Y, Zhu X, Wang C, Liu Q . Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling. Aging (Albany NY). 2019; 11(21):9643-9660. PMC: 6874452. DOI: 10.18632/aging.102410. View

19.

Fukui M, Choi H, Wang P, Zhu B . Mechanism underlying resveratrol's attenuation of paclitaxel cytotoxicity in human breast cancer cells: Role of the SIRT1-FOXO1-HER3 signaling pathway. Cancer Treat Res Commun. 2021; 28:100386. DOI: 10.1016/j.ctarc.2021.100386. View

20.

Liu H, Li Q, Cheng X, Wang H, Wang G, Hao H . UDP-glucuronosyltransferase 1A determinates intracellular accumulation and anti-cancer effect of β-lapachone in human colon cancer cells. PLoS One. 2015; 10(2):e0117051. PMC: 4333567. DOI: 10.1371/journal.pone.0117051. View