DNAJC12 promotes lung cancer growth by regulating the activation of β‑catenin.

Abstract

Lung cancer has become the leading cause of cancer‑associated mortality worldwide. However, the underlying mechanisms of lung cancer remain poorly understood. DnaJ heat shock protein family (HSP40) member C12 (DNAJC12) is a type III member belonging to the HSP40/DNAJ family. The role of DNAJC12 in numerous types of cancer has been previously reported; however, the effect of DNAJC12 in lung cancer remains unknown. The results of the present study indicated that DNAJC12 may be involved in lung cancer proliferation and migration by regulating the β‑catenin signaling pathway. Data generated in the present study and from The Cancer Genome Atlas revealed that the DNAJC12 expression levels were significantly upregulated in lung cancer tissues compared with non‑cancer lung tissues. The expression of DNAJC12 was subsequently knocked down in A549 and NCI‑H1975 lung cancer cells using lentiviral transfections and further experiments demonstrated that the knockdown of DNAJC12 inhibited the proliferation, colony formation, migration and invasion of lung cancer cells. The results of flow cytometric assays also revealed that the knockdown of DNAJC12 induced the apoptosis of lung cancer cells. In addition, the effects of DNAJC12 knockdown on the in vivo growth of lung cancer cells were observed. Signaling pathway analysis revealed that the knockdown of DNAJC12 expression suppressed the phosphorylation of p65 NF‑κB, downregulated the expression levels and inhibited the subsequent activation of β‑catenin, and downregulated the expression levels of vimentin. Rescue experiments demonstrated that the overexpression of β‑catenin, but not that of NF‑κB or vimentin, reversed the effects of DNAJC12 knockdown on the proliferation and invasion of lung cancer cells. On the whole, the findings of the present study suggest that DNAJC12 may play a crucial role in lung cancer tumorigenesis by regulating the expression and activation of β‑catenin. Therefore, DNAJC12 may represent a novel target for the treatment of lung cancer.

• Authors: Yun Li, Meng Li, Fengqi Jin, Jianbo Liu, Minghui Chen, Jingjing Yin
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 47 Issue 6 (Jun 2021) ISSN: 1791-244X [Electronic] Greece
• PMID: 33907820 (Publication Type: Journal Article)

Chemical References

• DNAJC12 protein, human
• NF-kappa B
• RNA, Messenger
• Repressor Proteins
• Vimentin
• beta Catenin

Topics

• Adult
• Aged
• Animals
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• RNA, Messenger (genetics, metabolism)
• Repressor Proteins (metabolism)
• Signal Transduction
• Tumor Stem Cell Assay
• Up-Regulation (genetics)
• Vimentin (metabolism)
• beta Catenin (metabolism)
• Mice