title: ÐÐ»Ð¸ÑÐ½Ð¸Ðµ ÑÐ±Ð¸ÐºÐ²Ð¸ÑÐ¸Ð½Ð»Ð¸Ð³Ð°Ð·Ñ Pirh2 Ð½Ð° Ð¼ÐµÑÐ°Ð±Ð¾Ð»Ð¸Ð·Ð¼ ÐºÐ»ÐµÑÐ¾Ðº ÑÐ°ÐºÐ° Ð»ÑÐ³ÐºÐ¾Ð³Ð¾ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ°
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð±Ð°ÐºÐ°Ð»Ð°Ð²ÑÐ°
titleType: Subtitle
title: The effect of ubiquitin ligase Pirh2 on the metabolism of human lung cancer cell lines
Creators: name: ÐÐ²Ð°Ð½Ð¸ÑÐ¸Ð½Ð°, ÐÐ»Ð¸Ð½Ð°
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2023
Subjects: E3-ÑÐ±Ð¸ÐºÐ²Ð¸ÑÐ¸Ð½Ð»Ð¸Ð³Ð°Ð·Ð° Pirh2
Ð¿ÑÐ¾ÑÐµÐ°ÑÐ¾Ð¼Ð½Ð°Ñ Ð´ÐµÐ³ÑÐ°Ð´Ð°ÑÐ¸Ñ Ð±ÐµÐ»ÐºÐ¾Ð²
Ð½ÐµÐ¼ÐµÐ»ÐºÐ¾ÐºÐ»ÐµÑÐ¾ÑÐ½Ð°Ñ ÐºÐ°ÑÑÐ¸Ð½Ð¾Ð¼Ð° Ð»ÐµÐ³ÐºÐ¾Ð³Ð¾
ÑÐµÑÐ¼ÐµÐ½ÑÑ Ð³Ð»Ð¸ÐºÐ¾Ð»Ð¸Ð·Ð°
Ð¼ÐµÐ¼Ð±ÑÐ°Ð½Ð½ÑÐ¹ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð» Ð¼Ð¸ÑÐ¾Ñ Ð¾Ð½Ð´ÑÐ¸Ð¹
3-Ð±ÑÐ¾Ð¼Ð¿Ð¸ÑÑÐ²Ð°Ñ
E3 ubiquitin ligase Pirh2
proteasome-dependent protein degradation
non-small cell lung carcinoma
glycolysis enzymes
mitochondrial membrane potential
3-brompyruvate

description: Ð Ð°Ðº Ð»ÐµÐ³ÐºÐ¸Ñ â ÑÑÐ¾ ÑÑÐµÑÐ¸Ð¹ Ð¿Ð¾ ÑÐ°ÑÐ¿ÑÐ¾ÑÑÑÐ°Ð½ÐµÐ½Ð½Ð¾ÑÑÐ¸ ÑÐ°Ðº Ð¿Ð¾ÑÐ»Ðµ ÑÐ°ÐºÐ° Ð¼Ð¾Ð»Ð¾ÑÐ½Ð¾Ð¹ Ð¸ Ð¿ÑÐµÐ´ÑÑÐ°ÑÐµÐ»ÑÐ½Ð¾Ð¹ Ð¶ÐµÐ»ÐµÐ·, Ð¾Ð´Ð½Ð°ÐºÐ¾ Ð½Ð° Ð½ÐµÐ³Ð¾ Ð¿ÑÐ¸ÑÐ¾Ð´Ð¸ÑÑÑ Ð½Ð°Ð¸Ð±Ð¾Ð»ÑÑÐ°Ñ Ð´Ð¾Ð»Ñ Ð²ÑÐµÑ ÑÐ¼ÐµÑÑÐµÐ¹, ÑÐ²ÑÐ·Ð°Ð½Ð½ÑÑ Ñ ÑÐ°ÐºÐ¾Ð¼. Ð¢ÐµÐ¼ Ð½Ðµ Ð¼ÐµÐ½ÐµÐµ, Ð·Ð° Ð¿Ð¾ÑÐ»ÐµÐ´Ð½Ð¸Ðµ Ð³Ð¾Ð´Ñ Ð±ÑÐ»Ð¸ Ð´Ð¾ÑÑÐ¸Ð³Ð½ÑÑÑ Ð²Ð°Ð¶Ð½ÑÐµ ÑÑÐ¿ÐµÑÐ¸ Ð² Ð´Ð¸Ð°Ð³Ð½Ð¾ÑÑÐ¸ÐºÐµ Ð¸ Ð»ÐµÑÐµÐ½Ð¸Ð¸ ÑÐ°ÐºÐ° Ð»ÐµÐ³ÐºÐ¸Ñ, ÑÑÐ¾ Ð¿ÑÐ¸Ð²ÐµÐ»Ð¾ Ðº Ð·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½ÑÐ¼ ÑÐ»ÑÑÑÐµÐ½Ð¸ÑÐ¼ Ð¸ ÑÐ²ÐµÐ»Ð¸ÑÐµÐ½Ð¸Ñ Ð¿ÑÐ¾ÑÐµÐ½ÑÐ° Ð²ÑÐ¶Ð¸Ð²Ð°ÐµÐ¼Ð¾ÑÑÐ¸. ÐÐ´Ð½Ð¾Ð¹ Ð¸Ð· Ð³Ð»Ð°Ð²Ð½ÑÑ ÑÑÑÐ°ÑÐµÐ³Ð¸Ð¹ Ð»ÐµÑÐµÐ½Ð¸Ñ Ð¾Ð½ÐºÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ñ Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ð¹ ÑÐ²Ð»ÑÐµÑÑÑ ÑÐ°ÑÐ³ÐµÑÐ½Ð°Ñ ÑÐµÑÐ°Ð¿Ð¸Ñ, ÐºÐ¾ÑÐ¾ÑÐ°Ñ Ð¿Ð¾Ð´Ð±Ð¸ÑÐ°ÐµÑÑÑ Ð¸Ð½Ð´Ð¸Ð²Ð¸Ð´ÑÐ°Ð»ÑÐ½Ð¾ Ð´Ð»Ñ ÐºÐ°Ð¶Ð´Ð¾Ð³Ð¾ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ° Ð½Ð° Ð¾ÑÐ½Ð¾Ð²Ð°Ð½Ð¸Ð¸ Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾-Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¸Ñ ÑÐ°ÑÐ°ÐºÑÐµÑÐ¸ÑÑÐ¸Ðº Ð¾Ð¿ÑÑÐ¾Ð»Ð¸. ÐÐ¼ÐµÐ½Ð½Ð¾ Ð¿Ð¾ÑÑÐ¾Ð¼Ñ Ð²Ð°Ð¶ÐµÐ½ Ð´Ð°Ð»ÑÐ½ÐµÐ¹ÑÐ¸Ð¹ Ð¿Ð¾Ð¸ÑÐº Ð¿ÑÐ¾Ð³Ð½Ð¾ÑÑÐ¸ÑÐµÑÐºÐ¸Ñ Ð¼Ð°ÑÐºÐµÑÐ¾Ð² Ð¸ Ð½Ð¾Ð²ÑÑ Ð¼Ð¸ÑÐµÐ½ÐµÐ¹ Ð´Ð»Ñ Ð¿Ð¾Ð²ÑÑÐµÐ½Ð¸Ñ ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾Ð¾Ð¿ÑÑÐ¾Ð»ÐµÐ²Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸Ð¸. Ð ÐºÐ°ÑÐµÑÑÐ²Ðµ Ð±Ð¸Ð¾Ð¼Ð°ÑÐºÐµÑÐ° Ð¸Â  Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½Ð¾Ð¹ Ð¼Ð¸ÑÐµÐ½Ð¸ Ð´Ð»Ñ ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐºÐ¸ ÑÐ°ÑÐ³ÐµÑÐ½Ð¾Ð¹ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾ÑÐ°ÐºÐ¾Ð²Ð¾Ð¹ ÑÐµÑÐ°Ð¿Ð¸Ð¸ Ð¼Ð¾Ð¶ÐµÑ ÑÐ°ÑÑÐ¼Ð°ÑÑÐ¸Ð²Ð°ÑÑÑÑ Ð±ÐµÐ»Ð¾Ðº Pirh2. Ð¯Ð²Ð»ÑÑÑÑ E3-ÑÐ±Ð¸ÐºÐ²Ð¸ÑÐ¸Ð½Ð»Ð¸Ð³Ð°Ð·Ð¾Ð¹ Ð´Ð»Ñ Ð¼Ð½Ð¾Ð³Ð¸Ñ Ð¾Ð½ÐºÐ¾-Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ Ð±ÐµÐ»ÐºÐ¾Ð², Pirh2 Ð¸Ð³ÑÐ°ÐµÑ Ð·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½ÑÑ ÑÐ¾Ð»Ñ Ð² ÐºÐ°Ð½ÑÐµÑÐ¾Ð³ÐµÐ½ÐµÐ·Ðµ ÐºÐ»ÐµÑÐ¾Ðº Ð»ÐµÐ³ÐºÐ¾Ð³Ð¾. ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ ÑÐ¾Ð»Ð¸ E3-ÑÐ±Ð¸ÐºÐ²Ð¸ÑÐ¸Ð½Ð»Ð¸Ð³Ð°Ð·Ñ Pirh2 Ð² ÑÐµÐ³ÑÐ»ÑÑÐ¸Ð¸ Ð¼ÐµÑÐ°Ð±Ð¾Ð»Ð¸Ð·Ð¼Ð° ÐºÐ»ÐµÑÐºÐ¾Ðº ÑÐ°ÐºÐ° Ð»ÐµÐ³ÐºÐ¾Ð³Ð¾. ÐÑÐ¸ Ð¿Ð¾Ð¼Ð¾ÑÐ¸ Ð²ÐµÑÑÐµÑÐ½-Ð±Ð»Ð¾Ñ Ð°Ð½Ð°Ð»Ð¸Ð·Ð° Ð¼Ñ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¸, ÑÑÐ¾ Ð½Ð¾ÐºÐ´Ð°ÑÐ½ Pirh2 ÑÐ¿Ð¾ÑÐ¾Ð±ÑÑÐ²ÑÐµÑ ÑÐ½Ð¸Ð¶ÐµÐ½Ð¸Ñ ÑÑÐ¾Ð²Ð½Ñ ÑÑÐ´Ð° ÑÐµÑÐ¼ÐµÐ½ÑÐ¾Ð² Ð³Ð»Ð¸ÐºÐ¾Ð»Ð¸Ð·Ð°, ÑÐ°ÐºÐ¸Ñ ÐºÐ°Ðº Ð³ÐµÐºÑÐ¾ÐºÐ¸Ð½Ð°Ð·Ð° 2, Ð°Ð»ÑÐ´Ð¾Ð»Ð°Ð·Ð° Ð Ð¸ Ð»Ð°ÐºÑÐ°ÑÐ´ÐµÐ³Ð¸Ð´ÑÐ¾Ð³ÐµÐ½Ð°Ð·Ð°, Ð¸ ÑÐµÐ³ÑÐ»Ð¸ÑÑÑÑÐ¸Ñ Ð´Ð°Ð½Ð½ÑÐµ ÑÐµÑÐ¼ÐµÐ½ÑÑ ÑÑÐ°Ð½ÑÐºÑÐ¸Ð¿ÑÐ¸Ð¾Ð½Ð½ÑÑ ÑÐ°ÐºÑÐ¾ÑÐ¾Ð² c-MyÑ Ð¸ HIF-1Î±. ÐÐ¾Ð»ÐµÐµ ÑÐ¾Ð³Ð¾, Ð¼Ñ Ð¾Ð±Ð½Ð°ÑÑÐ¶Ð¸Ð»Ð¸, ÑÑÐ¾ Ð¿Ð¾Ð´Ð°Ð²Ð»ÐµÐ½Ð¸Ðµ Pirh2 Ð² ÐºÐ»ÐµÑÐºÐ°Ñ Ð½ÐµÐ¼ÐµÐ»ÐºÐ¾ÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð¹ ÐºÐ°ÑÑÐ¸Ð½Ð¾Ð¼Ñ Ð»ÐµÐ³ÐºÐ¾Ð³Ð¾ Ð¿ÑÐ¸Ð²Ð¾Ð´Ð¸Ñ Ðº ÑÐ½Ð¸Ð¶ÐµÐ½Ð¸Ñ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð° Ð²Ð½ÑÑÑÐµÐ½Ð½ÐµÐ¹ Ð¼ÐµÐ¼Ð±ÑÐ°Ð½Ñ Ð¼Ð¸ÑÐ¾ÑÐ¾Ð½Ð´ÑÐ¸Ð¹, ÑÑÐ¾ ÑÐ°ÐºÐ¶Ðµ ÑÐ²Ð¸Ð´ÐµÑÐµÐ»ÑÑÑÐ²ÑÐµÑ Ð¾ ÑÐ½Ð¸Ð¶ÐµÐ½Ð½Ð¾Ð¼ Ð¼ÐµÑÐ°Ð±Ð¾Ð»Ð¸ÑÐµÑÐºÐ¾Ð¼ ÑÑÐ°ÑÑÑÐµ ÐºÐ»ÐµÑÐ¾Ðº. ÐÐ½Ð¾Ð¶ÐµÑÑÐ²Ð¾ Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ¾Ð², Ð¸ÑÐ¿Ð¾Ð»ÑÐ·ÑÐµÐ¼ÑÑ Ð² ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¾Ð¹ Ð¿ÑÐ°ÐºÑÐ¸ÐºÐµ Ð´Ð»Ñ Ð»ÐµÑÐµÐ½Ð¸Ñ Ð·Ð»Ð¾ÐºÐ°ÑÐµÑÑÐ²ÐµÐ½Ð½ÑÑ Ð½Ð¾Ð²Ð¾Ð¾Ð±ÑÐ°Ð·Ð¾Ð²Ð°Ð½Ð¸Ð¹, Ð½Ð°Ð¿ÑÐ°Ð²Ð»ÐµÐ½Ð¾ Ð½Ð° Ð¿Ð¾Ð´Ð°Ð²Ð»ÐµÐ½Ð¸Ðµ Ð¼ÐµÑÐ°Ð±Ð¾Ð»Ð¸Ð·Ð¼Ð° ÑÐ°ÐºÐ¾Ð²ÑÑ ÐºÐ»ÐµÑÐ¾Ðº. ÐÑ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¸, ÑÑÐ¾ Ð¿Ð¾Ð´Ð°Ð²Ð»ÐµÐ½Ð¸Ðµ Pirh2 Ð¿ÑÐ¸Ð²Ð¾Ð´Ð¸Ñ Ðº Ð¿Ð¾Ð²ÑÑÐµÐ½Ð¸Ñ ÑÑÑÐ¾Ð¹ÑÐ¸Ð²Ð¾ÑÑÐ¸ ÐºÐ»ÐµÑÐ¾Ðº ÑÐ°ÐºÐ° Ð»ÐµÐ³ÐºÐ¾Ð³Ð¾ Ðº Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÑ Ð³ÐµÐºÑÐ¾ÐºÐ¸Ð½Ð°Ð·Ñ 2, ÑÑÐ¾ ÑÐ¾Ð³Ð»Ð°ÑÑÐµÑÑÑ Ñ Ð²ÑÑÐ²Ð»ÐµÐ½Ð½Ð¾Ð¹ ÑÐ¾Ð»ÑÑ Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐ±Ð¸ÐºÐ²Ð¸ÑÐ¸Ð½Ð»Ð¸Ð³Ð°Ð·Ñ Ð² ÑÐµÐ³ÑÐ»ÑÑÐ¸Ð¸ Ð¼ÐµÑÐ°Ð±Ð¾Ð»Ð¸Ð·Ð¼Ð°. Ð¢Ð°ÐºÐ¸Ð¼ Ð¾Ð±ÑÐ°Ð·Ð¾Ð¼, Ð½Ð°Ð¼Ð¸ Ð±ÑÐ»Ð¾ ÑÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¾, ÑÑÐ¾ E3-ÑÐ±Ð¸ÐºÐ²Ð¸ÑÐ¸Ð½Ð»Ð¸Ð³Ð°Ð·Ð° Pirh2 Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÑÐµÑ Ð½Ðµ ÑÐ¾Ð»ÑÐºÐ¾ Ð¼ÐµÑÐ°Ð±Ð¾Ð»Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÑÐ°ÑÑÑ ÐºÐ»ÐµÑÐ¾Ðº ÑÐ°ÐºÐ° Ð»ÐµÐ³ÐºÐ¾Ð³Ð¾, Ð½Ð¾ ÑÐ°ÐºÐ¶Ðµ Ð¸Ñ Ð²Ð¾ÑÐ¿ÑÐ¸Ð¸Ð¼ÑÐ¸Ð²Ð¾ÑÑÑ Ðº Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ°Ð¼, Ð½Ð°Ð¿ÑÐ°Ð²Ð»ÐµÐ½Ð½ÑÐ¼ Ð½Ð° Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð³Ð»Ð¸ÐºÐ¾Ð»Ð¸Ð·Ð°.
description: Lung cancer is the third most widespread cancer after breast and prostate cancers, but it is the most common cause of cancer-related deaths. Nevertheless, important advances have been made in the diagnosis and treatment of lung cancer in recent years that has led to significant improvements and an increase in the survival rate. One of the main strategies of cancer treatment is targeted therapy, which is selected individually for each patient based on the results of molecular genetic analysis. Thus, the further investigation of prognostic markers and new targets is important to increase the effectiveness of anticancer therapy. Pirh2 protein can be considered a promising biomarker and potential target for anicancer therapy. Being the E3 ligase for many cancer-associated proteins Pirh2 plays an important role role in the tumorigenesis of lung cancer cells. This work is focused on the impact of E3-ubiquitin ligase Pirh2 in the regulation of lung cancer cell metabolism. We have shown that knockdown of Pirh2 decreased the expression of a number of glycolysis enzymes, such as hexokinase 2, aldolase A and lactate dehydrogenase, and transcription factors c-Myc and HIF-1Î± regulating these enzymes. Moreover, we found that the suppression of Pirh2 in non-small cell lung carcinoma cells leads to a decrease in the potential of the inner membrane of mitochondria, which also indicates a reduced metabolic status of cells. Many drugs used in clinical practice for the treatment of malignant neoplasms are targeted to the metabolism of cancer cells. As a result, we have demonstrated that cells with reduced expression of Pirh2 were more resistant to 3-brompyruvate treatment. Thus, we have discovered a novel role of E3-ubiquitin ligase Pirh2 not only in the regulation of the metabolic status of lung cancer cells, but also in the development of the resistance to antiglycolytic drugs.