KR101576053B1 - Biomarker for diagnosis of ovarian cancer cells - Google Patents

Abstract

The present invention relates to a method for diagnosing ovarian cancer by measuring the level of SRA1 in the body. In particular, the present invention is characterized in that the level of SRA1 lnc RNA is relatively measured in the RNA obtained from the patient's sample in order to provide information necessary for diagnosing ovarian cancer.

Description

{BIOMARKER FOR DIAGNOSIS OF OVARIAN CANCER CELLS}

The present invention relates to a method for diagnosing ovarian cancer by measuring the level of SRA1 in the body.

Female genitalia can be divided into external genitalia and internal genitalia in the pelvis. Internal genitalia refers specifically to vagina, uterus, fallopian tubes, ovaries and the like. Dual ovaries are present in pairs and are responsible for female reproductive capacity, releasing female hormones and discharging eggs every month. Female hormones secreted from the ovaries are estrogen and progesterone, which are characteristic of women.

Ovarian cancer is one of the most common female diseases, accounting for about 20% of gynecologic cancers, and is one of the most diagnosed cancers most often in patients. The majority of cases with no symptoms until the intra-abdominal metastasis after cancer have occurred are found in about two-thirds of cases at the initial diagnosis (more than three months). Therefore, the most common prognosis of female gynecologic cancer It is known as bad cancer. Because there is no effective screening method, women who have been diagnosed with ovarian cancer already have a considerable degree of cancer progression, and the probability of survival is very low.

About 60% of ovarian cancers are very rare, so if you have any symptoms, it is a good idea to have regular gynecological cancer screening once a year. The obstetrician will perform an earthquake to check whether the ovary is enlarged or touched, and if it is deemed necessary, the ovarian hump is checked by ultrasound. A blood test can also identify a tumor marker called CA125 to differentiate between benign and malignant tumors. Currently, CA125 is known as a diagnostic marker for ovarian cancer, and serum CA125 has been used for the differentiation and prognosis of ovarian cancer among benign and malignant ovarian masses (Zurawski, VR et al., Int. J. Cancer, 42: 677- 80, 1988; Vasilev SA et al., Obstet Gynecol. 71: 751-6, 1988; Rubin SC et al., Am J Obstet Gynecol. 160: 667-71, 1989; Bridgewater JA et al., J. Clin Oncol 17: 501-8,1999). However, CA125 is limited as a single marker because it tends to be elevated only in about half of women with stage I ovarian cancer. In general, both ultrasonography and CA125 detection are performed in parallel, but effective diagnostic methods for diagnosing ovarian cancer have not been developed yet.

New ovarian cancer markers such as CA15-3, CA19-9, OVX1, lysophosphatidic acid (LPA) and cancer embryo antigen (CEA) have been proposed, but these are also not sufficient to accurately diagnose ovarian cancer Currently, only CA 125 and ultrasonography are used together.

The diagnosis of ovarian cancer depends on the degree of spread of the disease. Stages are classified as follows. 1 st stage, the cancer stays in only one or both ovaries; Stage 2, cancer metastasis to the peritoneum of the ovary (tubal, uterine, rectal, bladder, etc.); Stage 3, metastasis to the peritoneum of the ovary (in the pelvis), to the epigastric and posterior peritoneal lymph nodes; Fourth, the cancer metastasized into the abdominal cavity or into the liver. In cases 1 and 2, the tumor can be completely removed by surgery, but in cases 3 and 4, it can not be completely removed by surgery alone. Therefore, it is defined as advanced cancer.

RNA directly involved in protein synthesis includes mRNA, tRAN, and rRNA. Non-coding RNAs, on the other hand, are RNAs that are transcribed from DNA but do not synthesize proteins. There are many kinds of non-coding RNAs, such as microRNA, siRNA, piRNA, etc. Among them, long non-coding RNAs with a length of 200 or more are referred to as lncRNAs and less than 200 are small ncRNAs (20-200 nt) do. nc RNAs is a major factor in gene regulation and influences general and cancer cell phenotypes by analysis of their function and clinical significance. Recent data indicate that over 3,000 human long invervening non-clding RNAs (lincRNAs) and most long ncRNAs are associated with DNA-binding proteins and epigenetically regulate the expression of multiple genes. Transcription of lncRNA is known to modulate gene activity in response to external oncogenic stimuli and DNA damage. This finding suggests a link between human disease, particularly cancer and lncRNA. Lnc RNA is recognized as a newly identified modulator in cancer development and cancer metastasis. Although the function of these RNAs and their mechanisms of expression are unknown, recent studies suggest that they are key to human cancer and disease.

Steroid receptor activator (SRA) RNA is a unique co-modulator that acts as a non-coding RNA. SRA is a nuclear receptor (NRs), myogenic differentiation 1 < / RTI > (MyoD) and co-inhibitors (corepressors) to allow lncRNA to act as a scaffold for the assembly / stability of co-regulator complexes. SRA RNA has been reported to be overexpressed during breast, ovarian, and bladder cancer generation and metastasis.

Accordingly, the present inventors have studied to develop a new diagnostic method capable of accurately diagnosing ovarian cancer early, and as a result, they confirmed that SRA1 in ovarian cancer is significantly elevated in ovarian cancer cells than in normal group.

Accordingly, an object of the present invention is to provide a novel biomarker for diagnosis of ovarian cancer.

In order to achieve the above object, the present invention provides a method of diagnosing ovarian cancer by measuring the level of SRA1.

The present invention also relates to a method for detecting the level of SRA1 lnc RNA by extracting RNA from a patient's sample in order to provide information necessary for diagnosis of ovarian cancer.

Wherein the relative level of SRA1 lnc RNA is measured.

Wherein the sample is selected from the group consisting of blood, serum, plasma, lymph fluid, cerebrospinal fluid, ascites, urine and tissue biopsy.

The present invention is a method for providing information necessary for diagnosis of ovarian cancer including the following steps:

(i) collecting a sample;

(ii) extracting RNA from the sample;

(iii) amplifying SRA1 lnc RNA in the extracted RNA; And

(iv) comparing the level of the normal group of SRA1 with the level of the SRA1 lnc RNA of the sample.

Wherein the RNA is lncRNA.

The step of amplifying the extracted RNA may use PCR.

The amplification conditions of SRA1 lncRNA in this PCR were initial denaturation at 95 ° C for 3 minutes; 40 cycles of denaturation at 95 ° C for 15 seconds, annealing at 60 ° C for 60 seconds, and elongation at 72 ° C for 60 seconds; And final elongation at 72 ° C for 5 minutes.

The PCR primer sequences used in the PCR may be selected from SEQ ID NOs: 1-4.

SEQ ID NO: 1: 5'-CTCCCTTCTTACCACCACCA-3 '(sense),

SEQ ID NO: 2: 5'-TGCAGATACACAGGGAGCAG-3 '(antisense);

SEQ ID NO: 3: U6 , 5'-CTCGCTTCGGCAGCACA-3 '(sense)

SEQ ID NO: 4: 5'-AACGCTTCAGGAATTTGCGT-3 '(antisense).

As another aspect of the present invention, a composition for treating ovarian cancer comprising siRNA represented by SEQ ID NO: 5 can be provided.

SEQ ID NO: 5: 5 '-CUC AUA ACA UGC AUU UCA AUU-3'

The siRNA represented by SEQ ID NO: 5 is characterized by blocking SRA1 lncRNA.

Thus, the present invention provides a novel method for diagnosing ovarian cancer. The present invention provides a novel biomarker capable of diagnosing ovarian cancer by SRA1.

Figure 1 is a graph showing the level of SRA1 expressed in human ovarian cancer.
Figure 2 is a graph showing the level of SRA1 expressed in various ovarian cancer cell lines.
FIG. 3 is a graph showing the growth of cells transfected with SRA1 gene-specific siRNA and negative control siRNA.
FIG. 4 is a photograph showing the migration and invasion of SRA1 in ovarian cancer cells. FIG. 4 (a) is a photograph showing the results of wound healing analysis for measuring the migration of cells transfected with the siRNA, This is a photograph showing the result of the Rigel invasion analysis.
FIG. 5 is a photograph and a graph showing the results of experiments in which SRA1 knockdown decreases MMP9 and VEGF expression, and (a) and (b) are photographs and graphs of western blot analysis for MMP-9 and VEGF expression, respectively.

Hereinafter, the present invention will be described in detail with reference to examples.

The present invention relates generally to biomarkers associated with ovarian cancer.

The present invention is based on the discovery that expression of SRA1 is expressed at a higher level in ovarian cancer tissues or cells than normal tissues. In particular, SRA1 is highly associated with metastasis in cancer cells and may serve as a specific marker for diagnosing ovarian cancer metastasis.

The term " ovarian cancer diagnostic marker " used in the present invention means a substance which is expressed in ovarian cancer tissues and cells and confirmed its expression, thereby showing a significant difference in a substance capable of confirming the onset of ovarian cancer, preferably normal and ovarian cancer tissues Quot; means an organic biomolecule such as protein or mRNA. In the present invention, the cancer diagnostic marker is lncRNA of SRA1 that expresses much more specifically than normal cells only in ovarian cancer tissues and cells, and it can be detected by a known detection method, for example, amplification, , The diagnosis of ovarian cancer can be made.

The term biological samples or samples used in the present invention include blood and other liquid samples of biologic origin, biopsy specimens, solid tissue samples such as tissue culture, or cells derived therefrom. More specifically, it may be a tissue, an extract, a cell lysate, a whole blood, a plasma, a serum, a saliva, an ophthalmic solution, a cerebrospinal fluid, a sweat, a urine, a milk, a plural liquid, a synovial fluid, a peritoneal fluid and the like. The sample can be obtained from an animal, preferably a mammal, most preferably a human. The sample can be pretreated prior to use in detection. For example, it may include filtration, distillation, extraction, concentration, inactivation of interfering components, addition of reagents, and the like. Further, nucleic acid and protein can be separated from the sample and used for detection.

In one embodiment of the present invention, SRA1 expression was increased in ovarian cancer. The expression of SRA1 lncRNA was measured by qRT-PCR in ovarian cancer tissues (n = 14) and corresponding normal tissues (n = 16). The expression of SRA1 in ovarian cancer tissues was 3.5 times higher (Fig. 1), indicating that SRA1 expression is unregulated in ovarian cancer.

In another embodiment of the present invention, siSRA1 was transfected into OVCA429 cells to observe cell proliferation. In other words, to determine the functional role of SRA1 in ovarian cancer, SRA1 expression was down-regulated using siRNA. For this purpose, SRA1 expression was first measured in ovarian cancer cell lines OVCAR3, SKOV3, TOV112D, OVCA433, and OVCA429 using qRT-PCR. As shown in Figure 2, SRA1 expression is higher in OVCA429, TOV112D, SKOV3 cells than in OVCA433 and OVCAR3 cells. Thus, OVCA429 cells with high SRA1 expression are used in SRA1 knockdown. To evaluate the efficiency of SRA1 gene-specific siRNA, cells were transfected with SRA1 siRNA for 24 hours, resulting in a 60% reduction in SRA1 RNA expression (Figure 3A). To investigate the role of SRA1 in ovarian cancer cell growth, siSRA1 transfected OVCA429 cells were used for CCK-8 analysis. In comparison with negative control siRNA, cell growth was reduced at 72 hours and 96 hours after siSRA1 transfection in OVCA429 cells transfected with siSRA1 (Fig. 3B). These results show that SRA1 is involved in the proliferation of ovarian cancer cells.

In addition, the present invention confirms the role of SRA1 in ovarian cancer cell migration and invasion in another embodiment . To determine the functional role of SRA1 on cell migration and invasion, siSRA1-transfected cells were used for wound healing and matrigel invasion assays, respectively. The extent of wound closure is greater in siRNA-infected cells than in siRNA negative control (siNC) -transfected cells (Fig. 4A). Thus, downregulation of SRA1 reduced the migration of ovarian cancer cells. The knockdown of SRA1 inhibited OVCA429 cell invasion by 95% or more (FIG. 4B). These results indicate that SRA1 increases the migration and invasion of ovarian cancer cells.

In ovarian cancer cell lines SRA1  Expression measurement

<1-1> Preparation of ovarian cancer cell line

<1-1-1> Human tissue

Ovarian cancer samples were obtained from 14 female patients who underwent surgery at Yonsei Severance Hospital between 2007 and 2012. Specimens from patients with coexisting gynecologic cancers were excluded from this study. (N = 16) as a control group. All specimens were quenched in liquid nitrogen and stored at -80 ° C until RNA extraction. This study was conducted on the basis of the Helsinki Declaration and was approved by the Yonsei Severance Hospital Ethics Committee.

<1-1-2> Cell culture

Human epithelial ovarian cancer cell lines OVCAR3, OVCA433, OVCA429, TOV112D and SKOV3 were cultured in Dulbecco's Modified Eagle Medium and HEK293 cells were cultured in RPMI-1640 medium (Gibco-BRL, Gaithersburg, MD, USA). The culture medium was supplemented with 10% (vol / vol) fetal bovine serum and penicillin / streptomycin. All cell lines were maintained at 37 ° C in a humidified atmosphere of 5% CO ₂ and 95% air. The number of cells used in all experiments did not exceed 20 passages.

<1-2> Quantitative real-time polymerase chain reaction (qRT-PCR)

The concentration of SRA1 lncRNA was measured. Total RNA was extracted from OVCA429 cell line and ovarian cancer samples and a tumor tissue sample (100 mg) using TRIzol® reagent (Invitrogen Corp., Carlsbad, Calif., USA) and total RNA was extracted using a reverse transcription reagent kit (Invitrogen) 2 &lt; / RTI &gt; of the cDNA was reverse transcribed to generate cDNA. 10 μl of SYBR® Green master PCR mix, 5 pmoles of each forward and reverse primer, 1 μl of diluted cDNA template, and the appropriate amount of template DNA using SYBR® Green Real-time PCR Kit (TOYOBO Co. Ltd, Osaka, Japan) QRT-PCR was performed in a 20-μl reaction volume containing sterile distilled water. The amplification conditions for SRA1 lncRNA were as follows: initial denaturation at 95 ° C for 3 min; 40 cycles of denaturation at 95 ° C for 15 seconds, annealing at 60 ° C for 60 seconds, and elongation at 72 ° C for 60 seconds; The final extension step at 72 ° C for 5 min was performed by qRT-PCR in the ABI StepOnePlus Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). All quantification was performed with U6. The PCR primer sequences are: SRA1 : 5'-CTCCCTTCTTACCACCACCA-3 '(sense), 5'-TGCAGATACACAGGGAGCAG-3'(antisense); and U6 , 5'-CTCGCTTCGGCAGCACA-3 '(sense), 5'-AACGCTTCAGGAATTTGCGT-3' (antisense). Relative gene expression was analyzed using the 2 △ ΔCT method and the results were expressed as the degree of change in the control group. The qRT-PCR experiment was repeated at least 3 times.

Expression of SRA1 lncRNA was measured using qRT-PCR in ovarian cancer tissues (n = 14) and corresponding normal tissues (n = 16). As a result, SRA1 expression in ovarian cancer tissues is about 3.5 times higher than in non-tumor tissues (Fig. 1). This suggests that the expression of SRA1 is unregulated in ovarian cancer.

Cell proliferation assay in ovarian cancer cell line

<2-1> Small interfering RNA (siRNA) transfection

SRA1 siRNA (siSRA1) and negative control siRNA (siNC) were purchased from Bioneer (Daejeon, Korea). OVCA429 cells (3 × 10 ⁵ cells / well) were inoculated into 6-well plates and transfected with 20 nM siRNA using G-Fectin Kit (Genolution Pharmaceuticals Inc., Seoul, Korea). These siRNA-transfected cells were used 48 hours after transfection for in vitro experiment analysis. The target sequence of SAR1 siRNA is as follows: siRNA, 5'-CUC AUA ACA UGC AUU UCA AUU -3 '

<2-2> Analysis of cell proliferation by SRA1 knockdown in ovarian cancer cell line

Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) assay (Dojindo Laboratories, Kumamoto, Japan). OVCA429 cells (1 × 10 ⁴ cells / well) were inoculated into 96-well flat bottom plates in 100 μL complete medium. The cells were incubated overnight by incubation with cells, and transfected with siNC or siSRA1 for 24, 48, 72 and 96 hours. CCK-8 solution (10 [mu] L) was added to each well, and the cells were incubated for an additional 2 hours. Absorbance was measured at 450 nm using a microplate reader. Independent experiments were repeated three times.

In order to determine the functional role of SRA1 in ovarian cancer, SRA1 expression was down-regulated using siRNA. For this purpose, SRA1 expression was first measured in ovarian cancer cell lines OVCAR3, SKOV3, TOV112D, OVCA433, and OVCA429 using qRT-PCR. As shown in Figure 2, SRA1 expression is higher in OVCA429, TOV112D, SKOV3 cells than in OVCA433 and OVCAR3 cells. Thus, OVCA429 cells with high SRA1 expression are used in SRA1 knockdown. To evaluate the efficiency of SRA1 gene-specific siRNA, cells were transfected with SRA1 siRNA for 24 hours, resulting in a 60% reduction in SRA1 RNA expression (Figure 3A). To investigate the role of SRA1 in ovarian cancer cell growth, siSRA1 transfected OVCA429 cells were used for CCK-8 analysis. In comparison with negative control siRNA, cell growth was reduced at 72 hours and 96 hours after siSRA1 transfection in OVCA429 cells transfected with siSRA1 (Fig. 3B). These results show that SRA1 is involved in the proliferation of ovarian cancer cells.

Ovarian cancer cell line SRA1 Cells by Mobile ability  Measure

OVCA429 cells transfected with siNC or siSRA1 (3 × 10 ⁵ cells / well) were inoculated on a 6-well culture plate with serum-containing medium and cultured to a cell density of about 90% confluence. The serum-containing medium was removed and the cells were not injected with serum for 24 hours. When the cell density was about 100% confluent, a monolayer was scrunched with a sterile 200-μL pipette tip to create an artificial equivalent wound. After scratching, the cells were washed with serum-free medium. Photographs of cell migration into the wound were taken at 0, 24 and 48 hours using a microscope. The analysis was repeated three times.

To determine the functional role of SRA1 for cell migration and invasion, siSRA1-transfected cells were used for wound healing assays. The extent of wound closure is greater in siSRA1-transfected cells than siNC-transfected cells (Fig. 4A). Thus, downregulation of SRA1 reduced the migration of ovarian cancer cells. These results show that SRA1 increases the ability of ovarian cancer cells to migrate.

Ovarian cancer cell line SRA1 Cells by Invasiveness  analysis

Matrigel invasion assays were performed using a BD Biocoat Matrigel Invasion Chamber (pore size: 8 mm, 24-well; BD Biosciences, Bedford, MA, USA). siSRA1-transfected cells and siNC-transfected OVCA429 cells (5 x 10 ⁴ cells / plate) were plated in serum-free medium in the upper chamber and complete medium was added to the lower chamber. A matrigel invasion chamber for 48 hours at 37 ° C 5% CO ₂ Lt; / RTI &gt; Non-invasive cells were removed from the upper chamber using a cotton swab. Cells invading through the pore were stained on the lower side of the filter (Diff Quik, Sysmes, Kobe, Japan). And these were counted using a hemocytometer. The analysis was repeated three more times.

To determine the functional role of SRA1 on cell invasion, siSRA1-transfected cells were used for matrigel invasion assays. Inhibited cell invasion by 95% or more in OVCA429 cells transfected with SRA1 as compared to negative control siRNA (Fig. 4B). These results show that SRA1 increases the invasion of ovarian cancer cells.

Ovarian cancer cell line SRA1  On by MMP -9 and VEGF  Regulation of expression

OVCA429 cells were transfected with siNC or siSRA1 for 48 hours, washed with cold 0.01 M PBS (pH 7.2), lysed with protease inhibitor (50 mM Tris-HCl [pH 7.4], 150 mM Saline, 1% Nonidet P-40, and 0.1% sodium dodecyl sulfate [SDS]). Protein concentrations were determined by the Bradford method (Bio-Rad Laboratories, Hercules, CA, USA) using the Bio-Rad protein assay reagent. Samples were boiled for 5 minutes, electrophoresed in 10% SDS-polyacrylamide gel, and transferred to a polyvinylidene difluoride membrane (Millipore, Billerica, MA, USA). The cells were then reacted for 1 hour at room temperature in 1 × Tris buffered saline (TBST; pH 7.6) solution containing 0.1% Tween 20 containing 5% skimmed milk powder. And reacted with the primary antibody overnight at 4 ° C with continued stirring. The primary antibodies used were mouse anti-human VEGF antibody (1: 1000 dilution; BD Biosciences), rabbit anti-human MMP-9 antibody (1: 1000 dilution; Cell Signaling, Beverly, Mass., USA) Human β-actin antibody (1: 10000 dilution; Sigma, St. Louis, Mo., USA). Membranes were washed 3 times with 1 x TBST and incubated with horseradish pericase-conjugated anti-rabbit secondary antibody (1: 3000 dilution; Abcam, Cambridge, MA, USA) or anti- 3000 dilution; Abcam) for 1 hour at room temperature. And then washed three times with 1 x TBST. Proteins were visualized using an enhanced chemiluminescence system (ECL ™; Amersham, Little Chalfont, UK) and band intensities were quantified using a Luminescent Image Analyzer (LAS-4000 mini, Fujifilm, Uppsala, Sweden). VEGF and MMP-9 expression were averaged by expression of [beta] -actin. Expression of VEGF and MMP-9 in siSRA1-transformed cells is expressed as a percentage of siNC-transfected cells (100%).

MMP-9 and VEGF play an important role in cancer progression by promoting migration and invasion. Thus, the effect of SRA1 on the expression level of these proteins is determined in OVCA429 cells. MMP-9 and VEGF protein expression was much lower in siSRA1-transfected cells than in siNC-transfected cells (FIGS. 5A and 5B). Taken together, these results demonstrate that SRA1 promotes ovarian cancer cell migration and invasion through upregulation of MMP-9 and VEGF expression.

<110> Industry-Academic Cooperation Foundation, Yonsei University <120> BIOMAREKR FOR DIAGNOSIS OF OVARIAN CANCER CELLS <130> 4635 <160> 5 <170> Kopatentin 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer for PCR <400> 1 ctcccttctt accaccacca 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer for PCR <400> 2 tgcagataca cagggagcag 20 <210> 3 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer for PCR <400> 3 ctcgcttcgg cagcaca 17 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer for PCR <400> 4 aacgcttcag gaatttgcgt 20 <210> 5 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> siRNA <400> 5 cucauaacau gcauuucaau u 21

Claims (9)

A method for detecting the level of homo sapiens steroid receptor activator 1 (SRA1) long non-coding RNA in RNA from a patient's sample to provide information needed to diagnose ovarian cancer.
The method according to claim 1,
Wherein the relative level of the homo sapiens steroid receptor activator 1 (SRA1) long non-coding RNA based on the level of the normal group of homo sapiens steroid receptor activator 1 (SRA1) is measured.
delete The method according to claim 1, wherein the level of long non-coding RNA is detected in a homo sapiens steroid receptor activator 1 (SRA1) comprising the steps of:
(i) extracting RNA from a sample of a patient;
(ii) amplifying homo sapiens steroid receptor activator 1 (SRA1) long non-coding RNA from the extracted RNA; And
(iii) comparing the level of the homo sapiens steroid receptor activator 1 (SRA1) in the normal group with the level of the homo sapiens steroid receptor activator 1 (SRA1) long non-coding RNA in the sample.
5. The method of claim 4, wherein amplifying the extracted RNA is performed using PCR.
6. The method according to claim 5, wherein the amplification conditions of SRA1 lncRNA in the PCR are initial denaturation at 95 ° C for 3 minutes; 40 cycles of denaturation at 95 ° C for 15 seconds, annealing at 60 ° C for 60 seconds, and elongation at 72 ° C for 60 seconds; And a final elongation at 72 ° C for 5 minutes.
7. The method according to claim 6, wherein the PCR primer sequence used in the PCR is one or more selected from the following SEQ ID NOS: 1 to 4.

SEQ ID NO: 1: 5'-CTCCCTTCTTACCACCACCA-3 '(sense),
SEQ ID NO: 2: 5'-TGCAGATACACAGGGAGCAG-3 '(antisense);
SEQ ID NO: 3: 5'-CTCGCTTCGGCAGCACA-3 '(sense)
SEQ ID NO: 4: 5'-AACGCTTCAGGAATTTGCGT-3 '(antisense).
A composition for treating ovarian cancer, comprising the siRNA represented by SEQ ID NO: 5.
SEQ ID NO: 5: 5 '-CUC AUA ACA UGC AUU UCA AUU -3'
9. The composition for treating ovarian cancer according to claim 8, wherein the siRNA represented by SEQ ID NO: 5 blocks homo sapiens steroid receptor activator 1 (SRA1) long non-coding RNA.

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