CN-122012503-A - Cancer-inhibiting small interfering RNA (ribonucleic acid) for simultaneously targeting oncogenes PTTG1 and STMN1 and application thereof

CN122012503ACN 122012503 ACN122012503 ACN 122012503ACN-122012503-A

Abstract

The invention relates to the technical field of biological medicine, and particularly discloses cancer-inhibiting small interfering RNA of simultaneous targeting oncogenes PTTG1 and STMN1 and application thereof, and the technical key point is that the sense strand sequence of the small interfering RNA is GGGAGAUCUCAAGUUUCAATT, and the antisense strand sequence is UUGAAACUUGAGAUCUCCCTT. The small interfering RNA of the invention can specifically silence the expression of PTTG1 and STMN1 simultaneously. Compared with the siRNA targeting a single gene (such as the siRNA aiming at ASCC3 or TRAPPC 4) in the prior art, the invention realizes the synergistic inhibition of tumor proliferation and metastasis paths through double targeting design, has more remarkable inhibition effect on tumor cell growth, has higher apoptosis induction efficiency and better in-vivo tumor inhibition effect compared with the method of physically mixing two single siRNAs, has the effect of effectively acting in various liver cancer cells and lasting action in animal models, and provides a core molecular entity for developing novel antitumor drugs.

Inventors

LI XIUHUA
HE ZHIYING
LIU CHANGCHENG
CAI YONGCHAO
SONG YANXIANG
JIANG DONG

Assignees

上海市东方医院（同济大学附属东方医院）

Dates

Publication Date: 20260512
Application Date: 20260309

Claims (5)

1. Meanwhile, the cancer-suppressing small interfering RNA of the targeted oncogenes PTTG1 and STMN1 is characterized in that the nucleotide sequence of the sense strand of the cancer-suppressing small interfering RNA is shown as SEQ ID NO.1, and the nucleotide sequence of the antisense strand is shown as SEQ ID NO. 2.
2. Use of small interfering RNAs according to claim 1 in the manufacture of a medicament for inhibiting a tumor.
3. The use according to claim 2, wherein the tumour is liver cancer.
4. Use according to claim 2 or 3, wherein the medicament is for inhibiting proliferation, migration and/or invasion of tumour cells.
5. The use according to any one of claims 2 to 4, wherein the medicament acts by simultaneously inhibiting expression of PTTG1 gene and STMN1 gene in tumor cells.

Description

Cancer-inhibiting small interfering RNA (ribonucleic acid) for simultaneously targeting oncogenes PTTG1 and STMN1 and application thereof Technical Field The invention relates to the technical field of biological medicines, in particular to cancer-inhibiting small interfering RNA for simultaneously targeting oncogenes PTTG1 and STMN1 and application thereof. Background Cancer is a malignant disease caused by abnormal proliferation of malignant cells, with invasive and metastatic properties. The incidence rate and the mortality rate of the cancer are high, and the cancer is a serious disease seriously harming the health of the national body. Abnormal activation of oncogenes by normal cells results in their transformation into malignant cells with unlimited proliferation capacity and invasion and metastasis capacity, which is the main cause of cancer occurrence. Malignant tumor cells are characterized by unlimited proliferation and invasive metastasis, and this series of malignant phenotypes is driven mainly by the synergistic activation of multiple oncogenes. Thus, inhibition of aberrant upregulated expression of these critical oncogenes is an effective strategy for reducing the proliferation and metastatic capacity of malignant cells. Among many oncogenes, pituitary tumor transforming gene 1 (PTTG 1) and microtubule depolymerizing protein (STMN 1) are of great interest. PTTG1 is an oncogene originally isolated from pituitary tumor cells, and is abnormally highly expressed in various cancers including liver cancer, and its high expression level is significantly associated with poor prognosis in patients. Studies show that tumor cells with high PTTG1 expression have stronger proliferation capacity, and reducing PTTG1 expression can effectively inhibit proliferation of tumor cells. STMN1 is a pro-cancerous phosphorylated protein that participates in tumor invasion and migration processes by regulating microtubule stability. STMN1 is also abnormally and highly expressed in various tumors, the high expression of the STMN1 is obviously positively correlated with metastasis and recurrence of tumors such as liver cancer, and the expression of the STMN1 can be knocked down to obviously inhibit migration and invasion capacity of malignant tumor cells. Small interfering RNA (siRNA) technology provides a powerful tool for targeted inhibition of specific gene expression. siRNA is a double-stranded RNA molecule of about 20-25 base pairs in length that specifically degrades target messenger RNA (mRNA) complementary to its sequence by an RNA interference (RNAi) mechanism, thereby efficiently and specifically precipitating expression of a target gene. Inhibition of oncogene expression using siRNA has proven to be an effective strategy for tumor intervention. Numerous studies have been conducted on the design of siRNA against a single oncogene in the prior art, and a large number of studies have been conducted to search for chinese patent publication No. CN115820632a which discloses siRNA targeting ASCC3 gene and its use in inhibiting proliferation, migration and invasion of bladder cancer, and chinese patent publication No. CN102899325A which discloses siRNA targeting trap 4 gene and its use in treating colorectal cancer by inhibiting ERK-MAPK pathway, all of which demonstrate the potential of siRNA against a single oncogene in specific cancer treatment. However, the occurrence and progression of malignant tumors is the result of multiple oncogene interactions, co-driven. Traditional siRNA blocking strategies against a single oncogene often have difficulty in completely inhibiting or reversing tumor growth, especially in dealing with both key biological processes of tumor proliferation and metastasis. Tumor cells have not only unlimited proliferation potential, but also invasive and migratory capabilities, and even by surgical excision of in situ lesions, the risk of tumor metastasis and recurrence remains high. Thus, inhibition of only a single oncogene (e.g., PTTG1 or STMN 1) cannot achieve a synergistic therapeutic effect of simultaneously and efficiently inhibiting tumor proliferation and metastasis. In view of the foregoing, there is a strong need in the art to develop a novel siRNA molecule capable of simultaneously and efficiently precipitating two critical and functionally complementary oncogenes, PTTG1 and STMN1, so as to overcome the limitations of the existing single-target siRNA technology and achieve more effective synergistic inhibition of tumor proliferation and metastasis. Therefore, the application provides cancer-suppressing small interfering RNA which simultaneously targets oncogenes PTTG1 and STMN1 and application thereof, so as to solve the problems. Disclosure of Invention The invention aims to solve the technical problems in the background technology and provide cancer-suppressing small interfering RNA for simultaneously targeting oncogenes PTTG1 and STMN1 and application thereof. The above object of