Tight Junction Protein 1 Suppresses Kidney Renal Clear Cell Carcinoma Cells Proliferation by Inducing Autophagy

Miao Li1,2, Di-Sheng Zhou1, Xin-Rong Shao1

  • 1Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.

Insights

Tight junction protein 1 (TJP1) is downregulated in kidney renal clear cell carcinoma (KIRC). TJP1 promotes autophagy, suppressing tumor growth and indicating a favorable prognosis for KIRC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Tight junction protein 1 (TJP1) has varied roles in cancer, but its function in kidney renal clear cell carcinoma (KIRC) is unknown.
  • TJP1 is an adaptor protein crucial for the adhesive barrier in cells.

Purpose of the Study:

  • To investigate the role of TJP1 in kidney renal clear cell carcinoma (KIRC).
  • To determine the prognostic significance of TJP1 in KIRC.
  • To elucidate the mechanism by which TJP1 affects KIRC progression, focusing on autophagy.

Main Methods:

  • Quantitative analysis of TJP1 expression in KIRC tissues versus normal tissues.
  • Correlation analysis between TJP1 expression, clinicopathological features (grade), and patient prognosis.
  • In vitro studies using KIRC cell lines (786-O, OS-RC-2) to assess TJP1's effect on autophagy signaling (autophagosome aggregation, LC3 II conversion).
  • Gene expression analysis of autophagy-related genes (BECN1, ATG3, ATG7) following TJP1 knockdown.
  • Functional assays evaluating the impact of TJP1 overexpression on cell proliferation and tumor growth, with and without autophagy inhibitors.

Main Results:

  • TJP1 expression was significantly downregulated in KIRC tissues compared to normal tissues.
  • Low TJP1 expression correlated with higher tumor grade and poorer prognosis in KIRC patients.
  • TJP1 induced autophagy signaling and was positively correlated with key autophagy-related genes (BECN1, ATG3, ATG7), which were associated with a good prognosis.
  • TJP1 overexpression suppressed KIRC cell proliferation and tumor growth, an effect attenuated by autophagy inhibition.

Conclusions:

  • TJP1 acts as a tumor suppressor in KIRC by inducing autophagy.
  • TJP1 represents a favorable prognostic biomarker for kidney renal clear cell carcinoma.
  • Targeting TJP1-mediated autophagy may offer a therapeutic strategy for KIRC.

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