Interference of Skp2 effectively inhibits the development and metastasis of colon carcinoma.

نویسندگان

  • Haijin Chen
  • Xiaodong Mo
  • Jinlong Yu
  • Shuxin Huang
  • Zonghai Huang
  • Liping Gao
چکیده

Colon cancer is a common type of malignancy in the digestive system. The aim of the present study was to investigate the role of S-phase kinase-associated protein 2 (Skp2) in colon carcinoma and to identify whether depletion of Skp2 by Skp2‑RNA interference (RNAi) attenuates the proliferation and migration of colon carcinoma. Three pairs of small interfering (si)RNA were designed based on the Skp2 gene sequence and the most effective one was used to silence the Skp2 gene in SW620 cells. Subsequent to the interference, quantitative polymerase chain reaction and western blot analysis were used for detecting the expression of Skp-2 mRNA and protein, respectively. The data demonstrated that the Skp2‑siRNA effectively inhibited proliferation (P<0.01), increased the levels of apoptosis and induced G0/G1 phase arrest of the SW620 cells (P<0.01). Transfection of the Skp2 siRNA into SW620 cells effectively reduced Skp2 protein levels, while p27 protein levels increased. In the in vivo experiments, a lentiviral vector of the Skp2-RNAi transfected into SW620 cells markedly inhibited Skp2 expression, as detected by immunohistochemical analysis of nude mice. Additionally, tumorigenicity experiments showed that inhibition of Skp2 significantly increased the survival rate of nude mice. Thus, the in vitro and in vivo results demonstrated that interference of Skp2 expression significantly inhibited the proliferation and induced the apoptosis of SW620 cells. This suggests that Skp2 protein has an important role in the progression of colon cancer. Therefore, Skp2 may enable the early diagnosis of colon cancer and provide new insights into molecular targets for cancer therapy.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The Usefulness of CytoFoam-Core in the Diagnosis of Thyroid Metastasis From Colon Cancer: A Case Report

Introduction: We report a case of a 64-year old man with a history of colon carcinoma. He underwent fine-needle aspiration by CytoFoam-core and diagnosis of metastatic colon cancer to the thyroid gland. Case presentation: In this case report, a solid thyroid nodule in the right lobe of a 64-year-old male was aspirated. The cytological smears showed a small group of atypical cells with the obvi...

متن کامل

The Usefulness of CytoFoam-Core in the Diagnosis of Thyroid Metastasis From Colon Cancer: A Case Report

Introduction: We report a case of a 64-year old man with a history of colon carcinoma. He underwent fine-needle aspiration by CytoFoam-core and diagnosis of metastatic colon cancer to the thyroid gland. Case presentation: In this case report, a solid thyroid nodule in the right lobe of a 64-year-old male was aspirated. The cytological smears showed a small group of atypical cells with the obvi...

متن کامل

A Rare Presentation of Colorectal Cancer with Unusual Progressive Intramuscular and Subcutaneous Metastatic Spread

Colorectal carcinoma is one of the most common causes of cancer-related death, worldwide. Recently, due to the introduction of novel imaging and therapeutic techniques, five-year survival of patients has increased. However, distant metastasis is still expected in half of the patients. Colorectal cancer tends to target the abdominal cavity, liver, lungs, and bones as the common sites of metastas...

متن کامل

Suppression of anoikis by SKP2 amplification and overexpression promotes metastasis of esophageal squamous cell carcinoma.

The gene of SKP2, located on chromosome 5p13, plays a critical role in cell cycle progression, especially at the G(1)-S transition, putatively through its control of several cell cycle regulator proteins including p27(kip1), p21(cip1), p57(kip2), p130, cyclin E, and c-Myc. Previous studies in this laboratory revealed that gain of chromosome 5p was often seen in esophageal squamous cell carcinom...

متن کامل

Small interfering RNA targeting of S phase kinase-interacting protein 2 inhibits cell growth of oral cancer cells by inhibiting p27 degradation.

S phase kinase-interacting protein 2 (Skp2), an F box protein, is required for the ubiquitination and consequent degradation of p27. It is well known that reduced expression of p27 is frequently observed in various cancers including oral squamous cell carcinoma and is due to an enhancement of its protein degradation. Our previous study showed that overexpression of Skp2 was frequently found in ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Molecular medicine reports

دوره 10 2  شماره 

صفحات  -

تاریخ انتشار 2014