Research Paper Volume 15, Issue 19 pp 10407—10427

PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma

Zhou Pan1, *, , Jing Huang2, *, , Huajie Song1, *, , Yusha Xiao3, , Ting Liu1, , Yan Zeng1, , Hengcheng Zhu1, , Kang Yang1, ,

  • 1 Department of Urology, Renmin Hospital of Wuhan University, Wuhan 443002, P.R. China
  • 2 Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan 443002, P.R. China
  • 3 Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 443002, P.R. China
* Equal contribution

Received: June 8, 2023       Accepted: September 9, 2023       Published: October 6, 2023
How to Cite

Copyright: © 2023 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Autophagy has been increasingly recognized as a critical regulatory mechanism in the maintenance of cellular homeostasis. A previous study showed that phospholipase C-like protein 1 (PLCL1) is associated with lipid metabolism in renal cell carcinoma (RCC). However, it is unclear whether PLCL1 regulates autophagy, thereby influencing the progression of RCC. Bioinformatics analysis of five microarray datasets revealed that expression of PLCL1 is decreased in tumours and is positively correlated with prognosis in RCC patients. Three independent public datasets, clinical RCC tissues and RCC cell lines, were validated using real-time qPCR, western blotting and immunohistochemistry. Using wound healing and transwell assays, we observed that elevated PLCL1 levels decreased the migratory distance and the invasive number of 786-O and ACHN cells, but PLCL1 knockdown reversed these changes in 769P cell lines compared to those in controls. The results of flow cytometry analysis indicated that PLCL1 promotes apoptosis. Moreover, transcriptional analysis based on stable overexpression of PLCL1 in 786-O cells revealed that PLCL1 is related to autophagy, and western blotting and autophagic experimental results further verified these findings. Mechanistic investigations confirmed that PLCL1 activates the AMPK/mTOR pathway and interacts with decidual protein induced by progesterone (DEPP). Collectively, our data suggest that PLCL1 functions as a suppressor of RCC progression by activating the AMPK/mTOR pathway, interacting with DEPP, initiating autophagy and inducing apoptosis. PLCL1 may be a promising therapeutic target for the diagnosis and treatment of ccRCC patients.


PLCL1: phospholipase C-like protein 1; RCC: Renal cell carcinoma; RT-qPCR: real-time qPCR; RCC: renal cell carcinoma; PIP2: phosphatidylinositol 4,5-bisphosphate; PI: phosphatidylinositol; IP3: 1,4,5-trisphosphate; UCP1: uncoupling protein 1; ATG: autophagy related gene; IRI: ischemia reperfusion injury; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; GEO: gene expression omnibus; TCGA: the cancer genome atlas; DEG: differential expression genes.