CN111518912A - Application of LINC02178 as diagnosis and treatment marker of cervical cancer - Google Patents

Abstract

The invention discloses an application of LINC02178 as a diagnosis and treatment marker of cervical cancer, and experiments prove that: LINC02178 is expressed in a low level in cervical cancer tissue compared to control tissue. The invention also discloses that LINC02178 can be used for preparing a medicine for treating cervical cancer. The research result of the invention provides a new cervical cancer clinical diagnosis method and simultaneously provides a new drug target for treating cervical cancer.

Description

Application of LINC02178 as diagnosis and treatment marker of cervical cancer

Technical Field

The invention relates to the field of biomedicine, in particular to application of LINC02178 as a diagnosis and treatment marker of cervical cancer.

Background

Cervical cancer is the most common gynecological malignancy, and is the first among female genital tumors. According to the 2014 statistical data of the world health organization, the number of new annual cases of cervical cancer is about 52.8 ten thousand, the number of annual deaths is about 26.6 ten thousand, 85% of the patients occur in developing countries, and rural areas are higher than cities. According to the latest Cancer statistical data published by the national tumor center, the number of new cases of cervical Cancer in China is about 9.89 ten thousand in 2015 years and the number of annual deaths is about 3.05 ten thousand in 2015 years, and the data shows a trend of rising year by year and the onset of disease younger [ Chen W, Zheng R, Baade P D, et al. The occurrence of cervical cancer is closely related to various factors, such as early marriage, early childbirth, prolificacy and sexual disturbance, but Human Papilloma Virus (HPV) infection is considered as a necessary condition for the onset of cervical cancer, HPV screening is positive in 99.7% of cervical cancer patients, and the risk of HPV persistent infection of patients suffering from cervical cancer is more than 250 times that of HPV-negative [ Wentzensen N, Arbyn M.HPV-based clinical cancer screening-factors, diagnosis, and missierceptions [ J ]. Prev Med,2017,98:33-35 l; torre L A, Islami F, Siegel R L, et al, Global Cancer in who: burden and tresds [ J ]. Cancer epidemic Biomarkers Prev,2017 ]. After the fact that HPV infection is the important cause of cervical cancer is firstly determined in the seven eighties of the last century, students carry out deep research on the mechanism of inducing the cervical cancer by HPV infection, and therefore, diagnosis methods and treatment strategies aiming at the cervical cancer are developed, including sensitive and specific precancerous diagnosis methods, targeted immunoprophylaxis measures and treatment methods, and the survival and life quality of cervical cancer patients are greatly improved.

With the development of modern biological detection technology and the continuous and deep research on the pathogenesis of tumors, various molecules in various biological processes related to tumorigenesis, such as nucleic acid, protein, carbohydrate, lipid, small molecule metabolites and even free tumor cells in blood, can be used as important tumor markers, and provide definite bases for clinical prevention, diagnosis and treatment. In cervical cancer, several tumor markers have been found to be used for clinical prevention of cervical cancer.

Ki-67 and p16INK4a are two common molecular markers for analyzing the proliferation state of tumor cells and the malignancy degree of tumors. Wherein Ki-67 is not expressed in silent GO phase cells but is highly expressed in G1, S, G2 and M phase cells, so it can be widely used to analyze the proliferative activity of cells to assess tumor progression [ Endl E, Gerdes J.the Ki-67protein: stimulating for and an unknown function [ J ] Exp Cell Res,2000,257(2): 231-; meanwhile, because the expression pedigree is wide, the tumor marker serving as a specific tumor marker still has certain defects, and other molecular markers are needed for auxiliary diagnosis in clinic. p16INK4a, a cyclin-regulating protein, specifically binds CDK4 and CDK6 to inhibit its activity and phosphorylation of downstream pRb, regulate cell cycle progression and cell differentiation processes; it has been found that p16INK4a expression is positively correlated with HR-HPV persistent infection and cervical tumor pathological grading, and has certain guiding value for patient post-operative HPV clearance and persistent infection [ Koh J, Enders G H, Dynlash B D, et al. Tumour-derived p16 alloys encoding proteins infection in cell-cycle inhibition [ J ] Nature,1995,375(6531): 506-.

The proExC antibody (BD Co.) specifically recognizes the nuclear protein MCM2 and the topoisomerase TOP2A complex induced by HPV infection. In cervical gland and squamous cell dysplasia, the cellular S-phase gene induced by the E7 oncogene promotes high expression of TOP2A and MCM2 in the nucleus, while TOP2A can combine with 6 MCM2 molecules to form a stable structure retained in the nucleus [ Santin A D, Zhan F, Bignoti E, et al. Gene expression profile of primary HPV16-and HPV 18-induced early stage receptors and nuclear specificity peptides: identification of non-catalytic molecular markers for nuclear specificity peptides and therapy [ J. Virology,2005,331 (269): 291) ]. Because it is not expressed in normal cervical epithelial cells, but is significantly highly expressed in HPV-induced squamous cells with active proliferation, it can be clinically used to distinguish atypical hyperplasia from similar changes such as incomplete squamous cell development or atrophy.

HPV DNA integrity and stability are mainly maintained by the capsid protein L1 and L2 together forming a stable protective shell. Among them, the L1 protein can also promote the invasion of virus particles into mucosal basement membrane zone cells or cervical epithelial cells by recognizing corresponding receptors on host cells. Expression of the L1 protein is continuously detected during mild to moderate dysplasia with HPV infection, but expression of the L1 protein gradually disappears as the degree of cervical carcinogenesis progresses [ McMurray H R, Mccanced J.human papillomavir type 16E6 organisms TERT gene transcription degradation of c-Myc and release of USF-mediated expression [ J ]. J Virol,2003,77(18): 9852-). Therefore, the disappearance of the expression of the HPV-L1 indicates that the viral genome is integrated in the host genome, and the diagnosis of the CIN3 stage of cervical cancer can be realized.

Lanminin-5 is a tumor marker closely related to tumor invasion, and the expression of the Lanminin-5 gene is closely related to the tumor progression in various malignant tumors. In the process of cervical cancer, the Lamin-5 is mainly expressed in the early stage of tumor, especially in the skin lesion of micro-infiltration, so that the method can be used for detecting the early stage of cervical squamous cell infiltration. MIB-I has an expression pattern similar to that of Ki-67, i.e., tumor cells that are active in a proliferative state with significantly high expression in stages of GINS, and detection in combination with Ki-67 can be used to assist in the analysis of the periodic state in which the tumor cells are located. Therefore, MIB-1 is another important indicator for detecting the proliferative activity of cells in the course of atypical hyperplasia.

In summary, although many tumor markers are currently used for clinical diagnosis of cervical cancer, tumor markers are constitutively expressed under normal conditions or increased in non-malignant tumor diseases, and thus lack tumor specificity. Therefore, the search of tumor specific antigens as biomarkers for the early diagnosis and prognosis determination of clinical cervical cancer is urgently needed.

Disclosure of Invention

According to one aspect of the invention, the invention provides the use of a product for detecting LINC02178 expression in the manufacture of a tool for diagnosing cervical cancer.

Further, the above-mentioned test products include: and detecting the expression level of LINC02178 by reverse transcription PCR, real-time quantitative PCR, in-situ hybridization, a chip or a high-throughput sequencing platform to diagnose the cervical cancer.

Further, the product for detecting the expression level of LINC02178 by reverse transcription PCR to diagnose cervical cancer at least comprises a pair of primers for specifically amplifying LINC 02178; the product for diagnosing the cervical cancer by detecting the expression level of the LINC02178 through real-time quantitative PCR at least comprises a pair of primers for specifically amplifying the LINC 02178; the product for detecting the expression level of LINC02178 to diagnose cervical cancer by in situ hybridization comprises: a probe that hybridizes to the nucleic acid sequence of LINC 02178; the product for detecting the expression level of LINC02178 to diagnose cervical cancer by using the chip comprises a probe hybridized with a nucleic acid sequence of LINC 02178.

In a specific embodiment of the invention, the product for diagnosing cervical cancer by detecting the expression level of LINC02178 through real-time quantitative PCR at least comprises a pair of primers for specifically amplifying LINC02178, wherein the primers are shown as SEQ ID NO.3 and SEQ ID NO. 4.

The present invention also provides a tool for diagnosing cervical cancer, which can diagnose cervical cancer by detecting the expression of LINC02178 in a sample.

Further, the tool comprises a chip, a kit, a test strip, or a high throughput sequencing platform.

Wherein the chip comprises a solid phase carrier and an oligonucleotide probe fixed on the solid phase carrier, and the oligonucleotide probe comprises an oligonucleotide probe aiming at LINC02178 and used for detecting the transcription level of LINC 02178; the kit comprises a reagent for detecting the transcription level of LINC 02178; the test paper comprises a reagent for detecting the transcription level of LINC 02178; the high throughput sequencing platform includes reagents for detecting LINC02178 transcript levels.

Still further, the agent for detecting the transcription level of LINC02178 comprises a primer and/or a probe for LINC 02178.

The probe that hybridizes to the nucleic acid sequence of LINC02178 may be DNA, RNA, a DNA-RNA chimera, PNA, or other derivatives. The length of the probe is not limited, and any length may be used as long as specific hybridization and specific binding to the target nucleotide sequence are achieved. The length of the probe may be as short as 25, 20, 15, 13 or 10 bases in length. Also, the length of the probe can be as long as 60, 80, 100, 150, 300 base pairs or more, even for the entire gene. Since different probe lengths have different effects on hybridization efficiency and signal specificity, the length of the probe is usually at least 14 base pairs, and at most, usually not more than 30 base pairs, and the length complementary to the nucleotide sequence of interest is optimally 15 to 25 base pairs. The probe self-complementary sequence is preferably less than 4 base pairs so as not to affect hybridization efficiency.

In a specific embodiment of the invention, the primer sequence for LINC02178 is as follows: the sequence of the forward primer is shown as SEQ ID NO.3, and the sequence of the reverse primer is shown as SEQ ID NO. 4.

Sources of LINC02178 for diagnosing cervical cancer include, but are not limited to, tissues and body fluids, including blood, interstitial fluid, and other in vivo fluid components in which DNA is present. In a specific embodiment of the invention, the source of LINC02178 for diagnosing cervical cancer is tissue.

The specific sequence of LINC02178(Gene ID:105371248) of the present invention can be found in the International public nucleic acid sequence database, GeneBank.

The present invention provides a pharmaceutical composition for treating cervical cancer, comprising an agent that promotes LINC 02178.

Further, the agent is not limited as long as it can promote the expression level of LINC02178 or promote the functional activity of LINC 02178.

The agent comprises an overexpression vector of LINC 02178.

The pharmaceutical composition of the present invention may be administered alone or together with other drugs as a medicine. The other drug that can be administered together with the pharmaceutical composition of the present invention is not limited as long as it does not impair the effect of the therapeutic or prophylactic pharmaceutical composition of the present invention.

The pharmaceutical composition of the invention can be prepared into various dosage forms according to requirements. Including, but not limited to, tablets, solutions, granules, patches, ointments, capsules, aerosols or suppositories for transdermal, mucosal, nasal, buccal, sublingual or oral use.

The route of administration of the pharmaceutical composition of the present invention is not limited as long as it can exert the desired therapeutic or prophylactic effect, and includes, but is not limited to, intravenous, intraperitoneal, intraocular, intraarterial, intrapulmonary, oral, intravesicular, intramuscular, intratracheal, subcutaneous, transdermal, transpleural, topical, inhalation, transmucosal, cutaneous, gastrointestinal, intraarticular, intraventricular, rectal, vaginal, intracranial, intraurethral, intrahepatic. In some cases, the administration may be systemic. In some cases topical administration.

The dosage of the pharmaceutical composition of the present invention is not limited as long as the desired therapeutic effect or prophylactic effect is obtained, and can be appropriately determined depending on the symptoms, sex, age, and the like. The dose of the therapeutic or prophylactic pharmaceutical composition of the present invention can be determined using, for example, the therapeutic effect or prophylactic effect on a disease as an index.

The invention also provides application of LINC02178 in preparing a medicine for treating cervical cancer.

The invention also provides application of the agent for promoting LINC02178 in preparing a medicine for treating cervical cancer.

Further, the medicament is defined as previously described.

In the context of the present invention, "diagnosing cervical cancer" includes both determining whether a subject has suffered from cervical cancer and determining whether a subject is at risk of suffering from cervical cancer.

Drawings

FIG. 1 shows a statistical graph for detecting differential expression of LncRNA in cervical cancer tissues and paracarcinoma tissues using QPCR.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings and examples. The following examples are intended to illustrate the invention only and are not intended to limit the scope of the invention. Experimental procedures without specific conditions noted in the examples, generally following conventional conditions, such as Sambrook et al, molecular cloning: the conditions described in the laboratory Manual (New York: Cold Spring harbor laboratory Press,1989), or according to the manufacturer's recommendations.

Example 1 study of abnormal expression of LncRNA in cancer tissues of cervical cancer patients

1. Tissue collection

43 cases of cervical squamous carcinoma tissues provided by obstetrics and gynecology department in hospitals were collected and originated from patients who were pathologically diagnosed as cervical squamous carcinoma after hysterectomy (conization or total resection), wherein paracancerous normal tissues were used as a control group. No immunosuppressive treatment, radiotherapy and chemotherapy were done before surgery in all cases.

2. Tissue RNA extraction

Taking cancer tissues cryopreserved at minus 80 ℃ and about 50mg of surrounding para-cancer tissues, putting the tissues into liquid nitrogen for grinding, transferring the tissues to a 1.5mL EP tube when no large-particle tissues exist, adding 1m L Trizol for total RNA extraction and real-time quantitative PCR analysis, and specifically carrying out the following steps:

1) adding 200 mu L of chloroform into the tissue suspension containing 1mL of Trizol, manually fully shaking and uniformly mixing, and standing at room temperature for 10 min;

2) centrifuging at 12000rpm and 4 deg.C for 15 min;

3) after the centrifugation is finished, the upper aqueous phase of the EP tube is gently absorbed into a new 1.5mL EP tube, 600 muL of isopropanol is added, the mixture is fully mixed by turning upside down, and the mixture is placed for 20min at room temperature (or placed for 2h at the temperature of minus 20 ℃ so as to increase the precipitation of RNA);

4) centrifuging at 12000rpm and 4 deg.C for 15 min;

5) discarding the supernatant, adding 75% ethanol diluted by DEPC water, and slightly blowing and sucking the suspension precipitate by a gun head;

6) centrifuging at 12000rpm and 4 deg.C for 15 min;

7) discarding the supernatant, sucking the residual liquid by using a gun head, and airing at room temperature for 5 min;

8) dissolving 20 μ L of RNAase-free water in the precipitate, and using or freezing at-80 deg.C for use.

3、QPCR

1) Reverse transcription reaction

Using FastQ μ ant cDNA first strand synthesis kit (cat # KR106) for IncRNA reverse transcription, genomic DNA removal reaction was first performed, 5 × g of DNA B μ ffer 2.0 μ l, total RNA 1 μ g, RNase Free ddH were added to the test tube₂O to make the total volume to 10 μ l, heating in water bath at 42 deg.C for 3 min.

10 × Fast RT B. mu.l, RT Enzyme Mix 1.0. mu.l, FQ-RT Primer Mix 2.0. mu.l, RNase Free ddH₂O5.0 μ l, mixing, adding into the above test tube, mixing to give 20 μ l, heating in water bath at 42 deg.C for 15min, and heating at 95 deg.C for 3 min.

2) Design and preparation of primers

The real-time quantitative PCR primer sequences used in the present application were as follows (designed and synthesized by Competition Biotechnology (Shanghai) Ltd.):

LINC01537 primer:

an upstream primer: 5'-AATGTTATGCCAGAGTCA-3' (SEQ ID NO.1),

a downstream primer: 5'-CCAGATTCCTACCTAAGAG-3' (SEQ ID NO. 2);

LINC02178 primer:

an upstream primer: 5'-CAGTCAGAAGCACATACA-3' (SEQ ID NO.3),

a downstream primer: 5'-CTAATGAAAGCCAGATAAAGG-3' (SEQ ID NO. 4);

GAPDH gene primers:

an upstream primer: 5'-GACCTGACCTGCCGTCTA-3' (SEQ ID NO.5),

a downstream primer: 5'-AGGAGTGGGTGTCGCTGT-3' (SEQ ID NO. 6).

3) Real-time quantitative PCR

Amplification was carried out using SuperReal PreMix Plus (SYBR Green) (cat # FP205) and the experimental procedures were performed according to the product instructions.

By using 2^-△△CtAnd analyzing the expression level of LncRNA by a relative quantification method, wherein Ct is the intensity value of a fluorescence signal detected in a reaction system by a thermal cycler. The calculation method comprises the following steps: Δ Δ Ct ═ (Ct target gene-Ct reference gene) cervical cancer tissue experimental group- (Ct target gene-Ct reference gene) control tissue group, 2^-△△CtThe expression of the target gene in the experimental group is shown as the fold change relative to the control group, and the analysis of the experimental data is performed by the Bio-RAD analysis software.

4. Statistical analysis statistical software SPSS19.0 is used for data analysis, and a pairing T test is used for judging whether the expression of LncRNA in a cervical cancer tissue sample and a paracancerous tissue sample has a difference in statistical significance. The statistical tests are bilateral tests, and the difference is statistically significant when P is less than 0.05.

5. Results

The target gene was normalized with the para-cancerous tissue as a reference, i.e., the relative expression level of the para-cancerous tissue was 1. Compared with the tissue beside cancer, the expression levels of LINC01537 and LINC02178 in the cervical cancer tissue are obviously reduced. The statistical results are shown in FIG. 1, and the differences are statistically significant (P < 0.05).

Example 2 study of relationship between LncRNA expression and proliferation, migration and invasion of cervical cancer cells

1. Cell culture

The Siha cells of human cervical carcinoma are routinely cultured in DMEM high-sugar medium containing 10% fetal calf serum at 37 ℃ and saturated humidity and containing 5% CO₂The culture box of (2) is subcultured, and cells in logarithmic growth phase are taken for experiment.

2. Overexpression vector construction

Specific primers are designed according to LncRNA sequence information in NCBI, corresponding LncRNA is obtained through amplification, amplified fragment gel is recovered and then is respectively connected with an expression vector pEGFP-C1 and then is transformed into DH5 alpha competent cells, and pEGFP-C1-LncRNA recombinant plasmids are obtained after positive cloning is selected and subjected to PCR and sequencing identification.

3. Cell transfection

2-3 × 10 before transfection in 1d⁵Cells were seeded in 6-well plates and transfected according to Lipofectamine3000 Liposome instructions when the degree of cell fusion reached 60% to 70%. Experiment set-up 2 groups: negative control group (pEGFP-C1, transfection of empty vector), pEGFP-C1-LncRNA overexpression group (transfection of LncRNA recombinant plasmid).

4. Cell transfection efficiency assay

The results of measurement of overexpression of the target gene by the QPCR method described in example 1 are shown in Table 1, and the differences among the groups are statistically significant (P < 0.05).

TABLE 1 plasmid transfection efficiency test

	pEGFP-C1 (relative expression amount)	pEGFP-C1-LncRNA (relative expression amount)
			LINC01537	0.9643±0.0249	7.382±0.9937
LINC02178	0.9643±0.0249	12.081±1.3402

5. Cell proliferation assay

The WST-1 method detects the influence of LncRNA expression on SiHa cell proliferation.

Adjusting cell density to 1 × 10²Mu.l, seeded in 96-well plates (100. mu.l/well) with 3 duplicate wells per set. 37 ℃ and 5% CO₂Culturing for 72h, adding 10 μ l WST-1, incubating for 2h, detecting optical density (D) value of cells at wavelength of 450nm with enzyme labeling instrument, and drawing cell proliferation curve according to D value.

The results are shown in table 2, with statistical significance for the differences between groups (P < 0.05). Shows that the cervical cancer cell proliferation can be inhibited after the expression of LINC01537 and LINC02178 is promoted.

TABLE 2 cervical cancer cell proliferation

5. Transwell experiment detection of influence of LncRNA expression on migration and invasion capacity of cervical cancer SiHa cells

Cell migration experiment 10. mu.l fibronectin (1. mu.g/. mu.l) was pipetted and spread evenly on the membrane of the lower chamber of the Transwell, the chamber was left at 37 ℃ for 4h, and the cell density was adjusted to 5 × 10 with DMEM medium without serum²Mu.l, 100. mu.l of the cell suspension was added to the upper chamber, and 600. mu.l of DMEM medium containing 20% FBS was added to the lower chamber, each of which was set to 3 duplicate wells. 37 ℃ and 5% CO₂After 48h incubation, non-migrated cells on the upper chamber membrane were gently wiped off with a cotton swab, washed 2 times with PBS and fixed in methanol for 30 min. After air-drying naturally, staining with 0.1% crystal violet for 20 min. Abandoning the dye liquor and double steamingThe total number of cells in 5 different fields, upper, lower, left, right, and middle, were counted under an optical microscope (× 200), averaged, and 3 times repeated.

Cell invasion assay: 200. mu.l of Matrigel collagen solution was diluted with 300. mu.l of serum-free medium DMEM. 100. mu.l of the diluted Matrigel gel was added to the upper chamber of the Transwell chamber and incubated in an incubator at 37 ℃ for 2 hours to solidify the Matrigel gel. The remaining steps were the same as for the migration experiment.

The results are shown in tables 3 and 4, with statistical significance for the differences between groups (P < 0.05). Shows that the cervical cancer cell migration and invasion can be inhibited after the expression of LINC01537 and LINC02178 is promoted.

TABLE 3 cervical cancer cell migration

	pEGFP-C1 (cell number)	pEGFP-C1-LncRNA (cell number)
			LINC01537	122.1±5.5	75.9±8.3
LINC02178	122.1±5.5	91±4.6

TABLE 4 cervical cancer cell invasion

	pEGFP-C1 (cell number)	pEGFP-C1-LncRNA (cell number)
			LINC01537	59±6	33.1±2.8
LINC02178	59±6	44.2±1.1

The experimental result shows that the composition can promote the expression of LINC01537 and LINC02178 and can be used for treating cervical cancer.

The above description of the embodiments is only intended to illustrate the method of the invention and its core idea. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications will also fall into the protection scope of the claims of the present invention.

Sequence listing

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Application of LINC02178 as cervical cancer diagnosis and treatment marker

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Claims (10)

1. The application of a product for detecting LINC02178 expression in preparing a tool for diagnosing cervical cancer; preferably, the product for diagnosing cervical cancer is a product for detecting the expression level of LINC02178 by reverse transcription PCR, real-time quantitative PCR, in situ hybridization, a chip, or a high-throughput sequencing platform.

2. The use of claim 1, wherein the product for diagnosing cervical cancer by reverse transcription PCR detection of LINC02178 expression level comprises at least one pair of primers for specific amplification of LINC 02178; the product for diagnosing the cervical cancer by detecting the expression level of the LINC02178 through real-time quantitative PCR at least comprises a pair of primers for specifically amplifying the LINC 02178; the product for detecting the expression level of LINC02178 to diagnose cervical cancer by in situ hybridization comprises: a probe that hybridizes to the nucleic acid sequence of LINC 02178; the product for detecting the expression level of LINC02178 to diagnose cervical cancer by using the chip comprises a probe hybridized with a nucleic acid sequence of LINC 02178.

3. The use of claim 2, wherein the product for diagnosing cervical cancer by detecting the expression level of LINC02178 by real-time quantitative PCR comprises at least one pair of primers for specifically amplifying LINC02178 as shown in SEQ ID No.3 and SEQ ID No. 4.

4. A tool for diagnosing cervical cancer, wherein said tool is capable of diagnosing cervical cancer by detecting expression of LINC02178 in a sample.

5. The tool of claim 4, wherein the tool comprises a chip, a kit, a strip, or a high throughput sequencing platform; preferably, the chip comprises a solid support and an oligonucleotide probe immobilized on the solid support, wherein the oligonucleotide probe comprises an oligonucleotide probe aiming at LINC02178 and used for detecting the transcription level of LINC 02178; the kit comprises a reagent for detecting the transcription level of LINC 02178; the test paper comprises a reagent for detecting the transcription level of LINC 02178; the high throughput sequencing platform includes reagents for detecting LINC02178 transcript levels.

6. The tool of claim 5, wherein the agent that detects the transcription level of LINC02178 comprises a primer and/or a probe for LINC 02178.

7. The tool of claim 6, wherein the primer sequence for LINC02178 is as follows: the sequence of the forward primer is shown as SEQ ID NO.3, and the sequence of the reverse primer is shown as SEQ ID NO. 4.

8. The tool of any one of claims 4-7, wherein the sample is tissue.

9. A medicament for treating cervical cancer, the medicament comprising an agent that promotes LINC02178, preferably, the agent that promotes LINC02178 comprises an overexpression vector for LINC 02178.

The application of LINC02178 in preparing the medicine for treating cervical cancer.

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